Effectiveness and safety of ombitasvir, paritaprevir, ritonavir ± dasabuvir ± ribavirin: An early access programme for Spanish patients with genotype 1/4 chronic hepatitis C virus infection.

Over the last 5 years, therapies for hepatitis C virus (HCV) infection have improved significantly, achieving sustained virologic response (SVR) rates of up to 100% in clinical trials in patients with HCV genotype 1. We investigated the effectiveness and safety of ombitasvir/paritaprevir/ritonavir±dasabuvir in an early access programme. This was a retrospective, multicentre, national study that included 291 treatment-naïve and treatment-experienced patients with genotype 1 or 4 HCV infection. Most patients (65.3%) were male, and the mean age was 57.5 years. The mean baseline viral load was 6.1 log, 69.8% had HCV 1b genotype, 72.9% had cirrhosis and 34.7% were treatment-naïve. SVR at 12 weeks posttreatment was 96.2%. Four patients had virological failure (1.4%), one leading to discontinuation. There were no statistical differences in virological response according to genotype or liver fibrosis. Thirty patients experienced serious adverse events (SAEs) (10.3%), leading to discontinuation in six cases. Hepatic decompensation was observed in five patients. Four patients died during treatment or follow-up, three of them directly related to liver failure. Multivariate analyses showed a decreased probability of achieving SVR associated with baseline albumin, bilirubin and Child-Pugh score B, and a greater probability of developing SAEs related to age and albumin. This combined therapy was highly effective in clinical practice with an acceptable safety profile and low rates of treatment discontinuation.

[Characteristics of atrial electrograms recorded in radiofrequency induced block lines in an experimental model]. / Características de los electrogramas auriculares registrados en las líneas de bloqueo producidas con radiofrecuencia en un modelo experimental.

AIM: To analyze and quantify atrial electrogram modifications following the induction of linear lesions in the atrial wall using radiofrequency ablation procedures. METHODS: An epicardial multiple electrode (221 unipolar electrodes) was used in 12 Langendorff perfused rabbit hearts to analyze atrial activation before and after radiofrequency induction of a linear lesion in the left atrial wall. After confirming the existence of conduction blockade in the lesion zone by epicardial mapping and propagation vector analysis, six electrodes each were selected in the lesioned and non-lesioned zones in all experiments, comparing the amplitude, maximum negative slope and morphology of the electrograms in both zones, before (control) and after radiofrequency delivery. RESULTS: Analysis of the reproducibility of the measurements in two consecutive cycles showed a variation of 1 +/- 5% for amplitude (NS) and 1 +/- 9% for maximum negative slope (NS). In the non-damaged zone, amplitude (105 +/- 22%) and slope (92 +/- 16%) (values normalized with respect to those recorded before radiofrequency) did not vary significantly following radiofrequency, and simple electrograms were the most frequent recordings (82 vs 83% in control; NS). Amplitude (19 +/- 7%, p < 0.001) and slope (24 +/- 11%; p < 0.001) decreased significantly in the lesion zone, as did the percentage of simple electrograms (6 vs 86% in control; p < 0,001). In this same zone the morphology could not be determined in 12% of the recordings, while multiple electrograms were obtained in 15% (vs 2% in control; p < 0.01), and the most frequent type corresponded to double electrograms (67 vs 12% in control, p < 0.001), with both components coinciding in time with atrial activation in the zones proximal and distal to the lesion line. CONCLUSIONS: Electrograms recorded directly in radiofrequency induce block lines show a significant decrease in amplitude and maximum negative slope. Double electrograms predominate in these recordings, both components of which represent activation on either side of the lesion. In a small proportion of cases simple and multiple electrograms can also be recorded in the block line.

[The activation patterns during atrial fibrillation in an experimental model]. / Patrones de activación durante la fibrilación auricular en un modelo experimental.

INTRODUCTION AND OBJECTIVES: In atrial fibrillation, along with the mechanisms of complete reentry and random activation focal activation patterns have been described which have been attributed both to propagation from the endocardium and to the existence of zones with automatic activity. The objectives of present study are to analyze and quantify the atrial activation patterns in an experimental model of atrial fibrillation. MATERIAL AND METHODS: In 11 Langendorff-perfused rabbit hearts atrial fibrillation was induced by atrial burst pacing after right atrial dilatation with an intra-atrial balloon. A multiple electrode consisting of 121 electrodes and positioned in the right atrial free wall was used to construct the activation maps corresponding to 10 segments of 100 ms in 11 different episodes of sustained atrial fibrillation (one per experiment). RESULTS: Of the 110 segments analyzed, 44 (40%) corresponded to random activation patterns. Fifteen segments (14%) corresponded to complete reentry, and in these cases the number of consecutive rotations ranged from 1 to 2.25 (mean 1.4 +/- 0.4). In 49 segments (44%) a single activation front was seen to pass through the recording area without block; alternatively, two simultaneous fronts were recorded that did not re-excite the zone activated by the other. In two segments (2%) there was a focal activation pattern without evidence of propagation from the epicardium surrounding the activated zone. CONCLUSIONS: a) in the experimental atrial fibrillation model used, random activation patterns are more frequent than complete reentry patterns; b) complete reentry can occur in areas smaller than 1 cm2, and c) focal activation during atrial fibrillation is rare.

[The assessment of cardiac involvement in a case of a thoracic injury from a firearm]. / Valoración de la afectación cardíaca en un caso de herida torácica por arma de fuego.

We report the case of a patient with a gunshot wound in the chest with a multiple small-caliber intrathoracic projectiles. The different noninvasive techniques employed to evaluate the anatomical location of these projectiles are discussed, together with their cardiac structural repercussions. The data provided by a simple chest X-ray, Computed Tomography (CT) and transthoracic echocardiography are commented on. A simple chest X-ray was unable to discern the location of the projectiles, in contrast to CT, which was able to identify both the number of projectiles and their location. The information provided was enhanced by transthoracic echocardiography, particularly in relation to those projectiles situated in anterior cardiac regions.

Esophageal inflammatory fibroid polyp. Endoscopic and radiologic features.

We present the case of a 60-year-old male patient, who had several episodes of melena during the last years. One month ago he had a new episode of digestive bleeding, and an endoscopic study was performed that showed at 35 cm from the dental arcade a polypoid, pedunculated lesion, with a diameter of 5 cm and a submucosal aspect, a few erosions on its surface and a fibrin deposit. Its head reached the cardia, and it bled when touched by the endoscope. The biopsies taken were negative. X-ray and CT studies confirmed the existence of a mass compatible with a submucosal lesion. The patient was operated and the tumor was excised. The histologic study showed an inflammatory fibroid polyp, an entity very rarely described at the level of the stomach, duodenum, small intestine, and colon and exceptionally described at the esophageal level.

Liver disease patterns in hemodialysis patients with antibodies to hepatitis C virus.

The present study correlated histopathology and diagnostic tests in hemodialysis patients with serologic markers for hepatitis C virus (HCV). Hepatitis C virus infection was found in 65 of 163 patients, as assessed by anti-c100-3 (ELISA 1), anti-c22-3, c33C (ELISA 2), and RIBA 2. Several histopathologic patterns were found in 33 liver samples from HCV-positive individuals: cirrhosis (n = 3), chronic active hepatitis (n = 14), chronic persistent hepatitis (n = 2), isolated hemosiderosis (n = 5), reactive hepatitis (n = 6), and others (n = 3). There was a positive correlation between time from the first aminotransferase peak and histologic damage (P = 0.015). However, the severity of liver disease did not correlate with the intensity of RIBA 2 positivity, mean levels or pattern of aminotransferases elevation, or markers of past hepatitis B virus infection. Moreover, aminotransferases were persistently normal in three patients with severe liver disease and were elevated in 10 patients with only mild changes. In 19 biopsied patients, the presence of plasma HCV RNA was examined by the polymerase chain reaction (PCR), which was positive in 15 of the 19 biopsy specimens. The ability of PCR positivity to predict the histologic severity of the disease was insufficient: four patients with minor liver damage had positive PCR and two patients with significant liver damage had negative PCR. No further correlations of PCR positivity were found with the other biochemical or immunologic markers of HCV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cancer of the middle third of the choledochus: an infrequent diagnosis]. / Cáncer de tercio medio de colédoco: un diagnóstico infrecuente.

We report the case of an 80-year-old woman with a previous history of HBP, hysterectomy due to cancer of the uterus and cholelithiasis, who was admitted in our hospital because of diffuse abdominal pain, marked jaundice, choluria and acholia during one week, together with anorexia and loss of weight. Blood chemistry results disclosed a total bilirubin of 11 mg/dl, a direct bilirubin of 8 mg/dl, GGTP 826 U/I, alkaline phosphatase 287 U/I, AST 285 U/I, ALT 837 U/I and LDH 242 U/I. The CA 19-9 marker was higher than 500 U/ml. The abdominal ultrasound examination did not show any space-occupying lesions; the extra and intrahepatic bile ducts were very dilated and the gall bladder showed multiple stones within its contents. The endoscopic retrograde cholangiopancreatography (ERCP) showed a homogeneous filiform defect at the middle third of the common bile duct of approximately 1 cm in length and with a marked dilatation of the bile ducts. A percutaneous drainage of the bile tree was performed, but the patient died.

[Eosinophilia and ascites as an expression of a subserous form of eosinophilic gastroenteritis]. / Eosinofilia y ascitis como expresión de una forma subserosa de gastroenteritis eosinofílica.

Clinical and biological features are discussed on a 50 years old female, who suffered a peritonitis with eosinophilic ascites, together with a bilateral pleural effusion with the same cytologic findings, developing in the course of an hypereosinophilia. The clinical situations in which eosinophilic ascites is associated with blood hypereosinophilia are reviewed. The histopathological findings in this case support the diagnosis of eosinophilic gastroenteritis of subserous type.

Long-term follow-up of hepatitis B chronic carriers who responded to interferon therapy.

We studied the long-term outcome of patients with chronic hepatitis B virus (HBV) infection who responded to interferon (IFN) therapy. Between 1983 and 1988, 120 patients were included in 5 different protocols; 94 patients were treated with IFN and 26 were controls. Loss of serum HBV-DNA was considered a partial response and occurred in 34 of the treated patients and in 10 of the controls. Only the partial-response patients were followed up for 14-64 months (mean 46 months). HBeAg disappeared in 32/34 of the partial-response treated patients and in 9/10 of the controls. During the follow-up period, 6/34 (18%) treated patients and 1/10 controls suffered a reactivation of the disease with reappearance of HBV-DNA. Only 8/34 (23%) treated patients and 1/10 of the controls lost HBsAg; no statistical differences were observed in baseline characteristics between HBsAg-negative patients and patients who remained HBsAg-positive. Of eight HBsAg-negative treated patients, four were serum HBV-DNA-negative upon polymerase chain reaction and thus formed the HBsAg-negative control cases. Although the frequency of HBsAg loss in treated patients is relatively low, the improvement in liver disease obtained from IFN therapy is sustained over a long period.

IgM antibody to hepatitis C virus in acute and chronic hepatitis C.

To assess possible role of testing for IgM-specific antibody in the diagnosis and monitoring of patients with hepatitis C, we tested sera from 14 patients with acute and 97 patients with chronic non-A, non-B hepatitis for IgG and IgM antibody to hepatitis C virus. IgG antibody to hepatitis C virus was detected in 93% of acute cases and 91% of chronic cases. Of the 101 patients with IgG antibody to hepatitis C virus, 57% had IgM antibody to hepatitis C virus. None of the 20 healthy subjects or 40 patients with acute or chronic hepatitis A or hepatitis B had IgM antibody to hepatitis C virus. At the onset of clinical symptoms in acute hepatitis C, IgG antibody to hepatitis C virus was detected in 8 (57%) and IgM antibody to hepatitis C virus in 9 of 14 patients (64%). Eventually, both IgG and IgM antibody to hepatitis C virus became detectable in 13 of 14 patients with acute hepatitis C. Seven patients with antibody to hepatitis C virus resolved the acute infection within 6 mo and all seven cleared IgM antibody to hepatitis C virus, whereas two cleared IgG antibody to hepatitis C virus. Six patients had a chronic outcome of the acute infection and IgM antibody to hepatitis C virus persisted in detectable amounts for more than 6 mo in all (mean = 15.5 mo). Among 88 patients with chronic non-A, non-B hepatitis with IgG antibody to hepatitis C virus, IgM antibody to hepatitis C virus was detected in 45 (51%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Reactivation of hepatitis B virus in chronic carriers with anti-HBe]. / Reactivación del virus B de la hepatitis en portadores crónicos con anti-HBe.

Thirty-eight hepatitis B virus (HBV) carriers, AgHBs and anti-HBe positive, with histologic diagnosis of chronic hepatitis have been periodically revised for three years. Three of them were homosexuals. Fourteen patients presented reactivation of viral replication characterized by the appearance in serum of HBV-DNA and an increase in transaminase levels. Only 7/27 (26%) presented spontaneous reactivation in contrast with 7/11 (64%) patients who had been treated with immunosuppression (p less than 0.05). Furthermore, in 3 cases free AgHBe was temporarily detected during reactivation. Histologic diagnosis and Knodell index were basically similar in reactivated patients and the rest. However, those who presented spontaneous reactivation presented a higher number of AgHB positive cells in liver tissue, both in nucleus and cytoplasm, than patients without reactivation, although, there were no significant differences in relation to the type of reactivation. In summary, this study suggests that immunosuppressants should not be given to HBV carriers with anti-HBe, since this would facilitate the reactivation of viral replication.

Detection of serum inhibitory factor for lymphocyte stimulation in chronic viral hepatitis: relationship with the replication level.

Sera from 111 patients with chronic viral hepatitis and from 55 cases with other liver disorders were assayed for serum inhibitory factor. The prevalence of this immunosuppressive factor was very similar between chronic hepatitis B (61%), chronic hepatitis delta (57%) and chronic hepatitis C (68%). At the same time, serum inhibitory factor was never detected in the other disorders studied. The presence of this inhibitory factor was detected in a significantly higher percentage (p less than 0.05) of HBeAg, HBV-DNA positive cases (75%) than in anti-HBe positive, HBV-DNA negative cases (44.4%). In chronic hepatitis delta, this immunosuppressive factor was also related to HDV-RNA positivity. The detection of this serum immunosuppressive factor in chronic viral hepatitis and its association with a high viral replication level implies a possible role of this factor in the immune pathogenic mechanism in infectious viral hepatitis.

High doses of recombinant alpha-interferon or gamma-interferon for chronic hepatitis C: a randomized, controlled trial.

Chronic hepatitis C is often a progressive liver disease for which there is no satisfactory treatment. We studied the efficacy of recombinant alpha-interferon or gamma-interferon in the treatment of this disease in comparison with a control group. Thirty patients were randomly assigned to three groups. Ten patients received 7.5 MU alpha-interferon/m2 body surface three times weekly for 3 mo, then 5 MU/m2 for 3 mo and 2.5 MU/m2 for 6 mo. Ten patients were treated with gamma-interferon at a dose of 2 MU/m2 for 6 mo and the other 10 served as controls without treatment. The mean serum ALT levels and liver histological findings improved significantly only in the patients treated with alpha-interferon. No changes were observed in patients treated with gamma-interferon or in controls. Five of 10 patients treated with alpha-interferon had complete responses (mean ALT normal during therapy). After treatment ALT returned to pretreatment levels in two of 5 patients. The long-term response rate after alpha-interferon therapy was 30% at 18 mo. We conclude that alpha-interferon is effective in controlling disease activity in a portion of patients with chronic hepatitis C. High doses of alpha-interferon do not appear to add further benefit in the response rate or relapse rate. gamma-Interferon therapy is ineffective.

Hepatitis delta virus RNA detection in chronic HBsAg carriers with and without HIV infection.

Hepatitis delta virus (HDV) RNA detection was carried out, using a full-length HDV RNA probe, in serum of 43 patients with chronic HDV infection. Among them, 30 cases (70%) were HDV RNA-positive. With respect to other HDV markers, serum HDAg (detected by immunoblot) was found in 33 patients (77%) and IgM anti-HD in 29 (67%). A similar percentage of HDV RNA-positive patients with and without circulating hepatitis B virus (HBV) DNA (32.5 vs. 37%, respectively) was found. Antibodies against the human immunodeficiency virus (HIV) were detected in 15/43 subjects studied. The presence of HDV RNA was significantly higher (p less than 0.05) in anti-HIV-seropositive cases (93%) than in the HIV-seronegative ones (57%). Moreover, simultaneous HDV and HBV replication was found more frequently (60 vs. 18%, p less than 0.05) and at higher levels among the anti-HIV-positive patients than in the rest. In addition, in most of the anti-HIV-positive subjects, HDV RNA and HBV DNA were constantly positive during a whole year of follow-up.