Background Bosentan is indicated in the treatment of pulmonary hypertension. Commonly reported adverse reactions are abnormal liver function (10.9%). Purpose To evaluate the risk of hepatotoxicity associated with bosentan, comparing incidence rates with the literature. Materials and methods Retrospective observational study, including all patients with pulmonary hypertension treated with bosentan between June 2003 and April 2013. Patients with previous liver disease were excluded as well as patients referred to other hospitals. Data collected included age, sex, liver aminotransferases (AST and ALT) before and during treatment and time until liver function changed. Normal levels in men were defined as AST 0–4 U/mL and ALT 0–40 U/mL. In women AST is 0–33 U/mL and ALT is 0–32 U/mL. Results The study described 32 patients treated with bosentan, six of whom were excluded: liver damage had been observed previously in 3 patients and no data in the other 3. The other 26 were 12 men and 14 women with a median age of 65.5 years (18–87 years). Serum transaminase levels were elevated to the upper limit normal (ULN) in 10 patients (38.5%). Measures taken were: dose reduction in 1 patient (3.8%), stop treatment in 6 patients (23.0%) and no change in 3 patients (11.5%). In all of them those increases were reversible on the next liver function monitored. Patients had a mean score, before starting treatment, of AST = 19.3 U/mL and ALT = 15.9 U/mL. Average values during treatment were AST = 34.2 U/mL and ALT = 33.4 U/mL. Mean highest levels in patients with hepatotoxicity were AST = 135.7 U/mL and ALT = 145.6 U/mL. In 7, elevation of transaminases occurred during the first 26 weeks of treatment. The median time of the event was 19 weeks (4–416 weeks). The incidence of abnormal increase in hepatic aminotransaminase levels was 38.5%. Conclusions The study describes a greater incidence of hepatotoxicity associated with bosentan than described in the literature. Treatment of these cases should be adjusted. Presence of bosentan and problems with increasing liver aminotransferases are relatively common and serum concentrations should be monitored during treatment. No conflict of interest.

BackgroundSome patients do not achieve successful results after treatment with older hepatitis C virus (HCV) antiviral drugs. We made a bibliographic research in PubMed and did not find any similar study in this area.PurposeTo assess the effectiveness of new direct acting antivirals (DAA) in previously treated HCV patients, and its relation to the type of previous treatment received.Material and methodsAn observational, descriptive, retrospective study of previously treated patients with HCV that ended their treatment with DAA before February 2016 was conducted. Patients were selected after online clinical history and from a pharmacy service database, analysing the following variables: genotype, degree of fibrosis, HIV coinfection, previous treatment, treatment using DAA, viral load at the end of treatment (VLET) and after 12 weeks (VR12).ResultsOf 250 patients that finished treatment, 160 (64%) had received previous treatment, 146 with pegylated interferon–ribavirin (INF-RBV) and 14 with first generation protease inhibitors (boceprevir/telaprevir). 16 patients had HIV coinfection. The distribution of patients according to genotype (G) was: 15 (9.37%) G4, 14 (8.7%) G3, 4 (2.5%) G1 untyped, 39 (24.37%) G1a and 88 (55%) G1b. According to the degree of fibrosis (F): 1 (0.62%) had F0, 8 (5%) F1, 34 (21.25%) F2, 35 (21.87%) F3 and 82 (51.25%) F4. Following the recommendations of the Clinical Practice Guidelines and the Strategic Plan of the Spanish NHS, 11 combinations of DAA were used (daclatasvir, ledipasvir, sofosbuvir, dasabuvir, ombitasvir, paritaprevir/r, simeprevir), ribavirin and pegylated interferon. VLET was undetectable in 100% of patients. Data were available concerning 121 patients after 12 weeks, 117 of whom (96.7%) maintained a sustained VR12 (SVR12). 4 patients (3.3%) who failed had been treated previously with INF-RBV; 2 had G1b F4, 1 had G1a F4 and 1 had G3 F2.ConclusionThe effectiveness of DAA in patients who had received previous treatment in clinical practice was within the percentages presented in clinical trials. Although there were too few failures in the treatment to conclude significant associations, there may be some relation between failures with DAA and pretreatment with INF-RBV. All patients who had not achieved SVR12 relapsed after an undetectable VLET.References and/or acknowledgementsAcknowledgements to Mireya Amat for the help offered.No conflict of interest