M. Testillano

Efficacy and safety of entecavir in clinical practice in treatment-naive Caucasian chronic hepatitis B patients.

Background Entecavir is an effective treatment for chronic hepatitis B. However, data from clinical practice are limited, especially in hepatitis B e antigen (HBeAg)-positive patients. Methods We retrospectively analysed data from 190 nucleos(t)ide-naive chronic hepatitis B patients treated with entecavir (0.5 mg/day) in 25 Spanish centres. Virological response (hepatitis B virus DNA <50 IU/ml by PCR), biochemical response (alanine aminotransferase ⩽1×upper limit of normal) and serological response were assessed at weeks 12, 24, 36 and 48. Results The cohort was 73% male, 84% Caucasian, and 30% HBeAg-positive. Thirty-four per cent of the patients who underwent biopsy had advanced fibrosis/cirrhosis. At baseline, the median hepatitis B virus DNA was 5.94 (interquartile range=4.64–7.39) log10 IU/ml. At week 48, 83% of the patients (61% HBeAg-positive; 92% HBeAg-negative) achieved a virological response and 82% (78% HBeAg-positive; 83% HBeAg-negative) of those with elevated baseline alanine aminotransferase showed a biochemical response. Twenty-six per cent (14/54) of the HBeAg-positive patients lost HBeAg and 22% (12/54) achieved seroconversion to anti-HBe. A significant correlation was observed between virological response at week 12 and the rate of seroconversion to anti-HBe at week 48 (P=0.039). This correlation was also noted at weeks 24, 36 and 48 (P=0.003, 0.002 and 0.017, respectively). Three patients (2%) showed clearance of hepatitis B surface antigen. No resistance to entecavir was observed. Treatment with entecavir was generally well tolerated. No patients discontinued treatment due to adverse events. Conclusion Entecavir monotherapy in clinical practice was well tolerated and resulted in a rapid and significant reduction in viral load. A virological response at week 12 correlated significantly with the rate of seroconversion to anti-HBe at week 48.

A comparison of survival in patients with hepatocellular carcinoma and portal vein invasion treated by radioembolization or sorafenib.

Sorafenib (SOR) is the standard of care for patients with hepatocellular carcinoma (HCC) and portal vein invasion (PVI), based on the results of phase 3 trials. However, radioembolization (RE) using yttrium‐90 microspheres has been shown to achieve higher response rates and better survival in large cohorts and phase 2 trials. This study aimed to compare survival of HCC patients with PVI treated by RE or SOR.

Clinical outcomes of patients undergoing antiviral therapy while awaiting liver transplantation

BACKGROUND & AIMS Antiviral therapy for the treatment of hepatitis C (HCV) infection has proved to be safe and efficacious in patients with cirrhosis awaiting liver transplantation (LT). However, the information regarding the clinical impact of viral eradication in patients on the waiting list is still limited. The aim of the study was to investigate the probability of delisting in patients who underwent antiviral therapy, and the clinical outcomes of these delisted patients. METHODS Observational, multicenter and retrospective analysis was carried out on prospectively collected data from patients positive for HCV, treated with an interferon-free regimen, while awaiting LT in 18 hospitals in Spain. RESULTS In total, 238 patients were enrolled in the study. The indication for LT was decompensated cirrhosis (with or without hepatocellular carcinoma [HCC]) in 171 (72%) patients, and HCC in 67 (28%) patients. Sustained virologic response (SVR) rate was significantly higher in patients with compensated cirrhosis and HCC (92% vs. 83% in patients with decompensated cirrhosis with or without HCC, p=0.042). Among 122 patients with decompensated cirrhosis without HCC, 29 (24%) were delisted due to improvement. No patient with baseline MELD score >20 was delisted. After delisting (median follow-up of 88weeks), three patients had clinical decompensations and three had de novo HCC. Only two of the patients with HCC had to be re-admitted onto the waiting list. The remaining 23 patients remained stable, with no indication for LT. CONCLUSIONS Antiviral therapy is safe and efficacious in patients awaiting LT. A quarter of patients with decompensated cirrhosis can be delisted asa result of clinical improvement, which appears to be remain stable in most patients. Thus, delisting is a safe strategy that could spare organs and benefit other patients with a more urgent need. LAY SUMMARY Antiviral therapy in patients awaiting liver transplantation is safe and efficacious. Viral eradication allows removal from the waiting list of a quarter of treated patients. Delisting because of clinical improvement is a safe strategy that can spare organs for patients in urgent need.

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.

Efficacy and safety of daclatasvir-based antiviral therapy in HCV recurrence after liver transplantation. Role of cirrhosis and genotype 3. A multi-centre cohort study

Direct‐acting antiviral agents (DAA) combining daclatasvir (DCV) have reported good outcomes in the recurrence of hepatitis C virus (HCV) infection after liver transplant (LT). However, its effect on the severe recurrence and the risk of death remains controversial. We evaluated the efficacy, predictors of survival, and safety of DAC‐based regimens in a large real‐world cohort. A total of 331 patients received DCV‐based therapy. Duration of therapy and ribavirin use were at the investigators discretion. The primary end point was sustained virological response (SVR) at week 12. A multivariate analysis of predictive factors of mortality was performed. Intention‐to‐treat (ITT) and per‐protocol SVR were 93.05% and 96.9%. ITT‐SVR was lower in cirrhosis (n = 163) (96.4% vs. 89.6% P = 0.017); the SVR in genotype 3 (n = 91) was similar, even in advanced fibrosis (96.7% vs. 88%, P = 0.2). Ten patients (3%) experienced virological failure. Therapy was stopped in 18 patients (5.44%), and ten died during treatment. A total of 22 patients (6.6%) died. Albumin (HR = 0.376; 95% CI 0.155–0.910) and baseline MELD (HR = 1.137; 95% CI: 1.061–1.218) were predictors of death. DCV‐based DAA treatment is efficacious and safe in patients with HCV infection after LT. Baseline MELD score and serum albumin are predictors of survival irrespective of viral response.

Neutrophil-to-lymphocyte ratio predicts survival in European patients with hepatocellular carcinoma administered sorafenib

Neutrophil-to-lymphocyte ratio (NLR) is considered a prognostic factor in patients with hepatocellular carcinoma (HCC). Our aim is to investigate the prognostic significance of NLR in patients with HCC treated with sorafenib. Results Median follow-up time was 7 months. Patients were mostly in the intermediate (27.3%) or advanced (72.7%) BCLC stages, 38.6% had vascular invasion and 27.5% extrahepatic disease. A large proportion (38.9%) had been previously treated with TACE. Liver function was preserved: 65.8% were classed as Child A. Median overall survival was 7.7 months (95% CI: 5.8–9.6). In univariate analysis, vascular invasion (P = 0.004), ECOG-PS ≥ 1 (P < 0.001), high bilirubin (P < 0.001), clinical ascites (P = 0.036), BCLC stage (P = 0.004), no previous TACE (P = 0.041) and NRL ≥ 2.3 (P = 0.005) were predictors of poor survival. Skin toxicity (P = 0.039) or hypertension (P = 0.033) during treatment were related to better survival. In multivariate analysis NLR ≥ 2.3 [HR 1.72 (95% CI: 1.03–2.71)], hyperbilirubinemia [HR 3.42 (95% CI: 1.87–6.25)] and ECOG-PS ≥ 1 [HR 1.97 (95% CI: 1.19–3.26)] were found as independent indicators of poor overall survival. Dermatologic adverse effects were an indicator of good overall survival [HR 0.59 (95% CI: 0.38–0.92)]. Material and Methods One hundred and fifty-four consecutive HCC patients treated with sorafenib in four different Spanish hospitals between August 2005 and October 2013 were analysed. Clinical, laboratory, and tumour features were obtained. Survival was calculated from the moment sorafenib treatment was initiated. Log-rank and Cox regression were used to analyse the ability of NLR to predict survival. Conclusions NLR is an independent prognostic indicator for overall survival in HCC patients treated with sorafenib.

Entecavir has high efficacy and safety in white patients with chronic hepatitis B and comorbidities.

Objectives The aim of this study was to evaluate the efficacy and safety of entecavir monotherapy in nucleos(t)ide-naive chronic hepatitis B patients and to analyse the influence of the comorbidity burden on therapy outcome. Methods We retrospectively analysed data from 237 nucleos(t)ide-naive chronic hepatitis B white patients treated with entecavir (0.5 mg/day) at 23 Spanish centres. For the efficacy and safety analyses, patients were grouped according to their baseline comorbidities. Results The mean age of the cohort was 43 years (range: 19–82 years); 73% were male, 83% were white, and 33% were hepatitis B e antigen (HBeAg) positive. At baseline, the median hepatitis B virus DNA level was 6.20 log10 IU/ml. Of the patients, 18% had cirrhosis, 9.7% had diabetes, 16.3% had hypertension, and 15.7% had obesity; 13.4% of patients had more than one comorbid condition. Virological and biochemical responses at month 36 were obtained independently of the patients’ baseline comorbid condition. Of 10 HBeAg-positive patients who discontinued treatment after HBeAg seroconversion, those who had not also cleared HBsAg (six) experienced virological recurrence in a median 5.6 months. There were no treatment discontinuations due to adverse events. Three patients were diagnosed with hepatocellular carcinoma at months 12, 30 and 54, and six experienced hepatic decompensation during follow-up. The median serum creatinine levels did not increase after 36 months of treatment, even in patients with comorbidities. Conclusion Entecavir is safe, well tolerated, and highly effective, even in patients with comorbid condition(s). Discontinuation of treatment in patients who have not been cleared of HBsAg may lead to virological recurrence.

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

Direct-acting antivirals are effective and safe in HCV/HIV-coinfected liver transplant recipients who experience recurrence of hepatitis C: A prospective nationwide cohort study

Direct‐acting antivirals have proved to be highly efficacious and safe in monoinfected liver transplant (LT) recipients who experience recurrence of hepatitis C virus (HCV) infection. However, there is a lack of data on effectiveness and tolerability of these regimens in HCV/HIV‐coinfected patients who experience recurrence of HCV infection after LT. In this prospective, multicenter cohort study, the outcomes of 47 HCV/HIV‐coinfected LT patients who received DAA therapy (with or without ribavirin [RBV]) were compared with those of a matched cohort of 148 HCV‐monoinfected LT recipients who received similar treatment. Baseline characteristics were similar in both groups. HCV/HIV‐coinfected patients had a median (IQR) CD4 T‐cell count of 366 (256‐467) cells/µL. HIV‐RNA was <50 copies/mL in 96% of patients. The DAA regimens administered were SOF + LDV ± RBV (34%), SOF + SMV ± RBV (31%), SOF + DCV ± RBV (27%), SMV + DCV ± RBV (5%), and 3D (3%), with no differences between the groups. Treatment was well tolerated in both groups. Rates of SVR (negative serum HCV‐RNA at 12 weeks after the end of treatment) were high and similar for coinfected and monoinfected patients (95% and 94%, respectively; P = .239). Albeit not significant, a trend toward lower SVR rates among patients with advanced fibrosis (P = .093) and genotype 4 (P = .088) was observed. In conclusion, interferon‐free regimens with DAAs for post‐LT recurrence of HCV infection in HIV‐infected individuals were highly effective and well tolerated, with results comparable to those of HCV‐monoinfected patients.