Presentation and Outcomes of Pregnancy in Patients With Autoimmune Hepatitis.

Autoimmune hepatitis (AIH) frequently affects women of childbearing age in whom the desire to have a family raises the question regarding the potential risks for the fetus and the mother. The information on AIH in pregnant patients is scarce.1 The aims of this study were (1) to identify the risk factors associated with flares in pregnant patients diagnosed with AIH, (2) to determine the course of AIH in patients with pregnancy-related flares, and (3) to describe the outcome of AIH diagnosed in the postpartum period.

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.

High efficacy and safety of triple therapy in HCV genotype 1 and moderate fibrosis: a multicenter study of clinical practice in Spain.

BACKGROUND AND RATIONAL: Telaprevir-based therapy (TBT) has been extensively evaluated in clinical trials. So we designed a study to compare the efficacy and safety of TBT between patients with moderate fibrosis and those suffering from advanced fibrosis in clinical practice. A multicenter observational and ambispective study was conducted. It included 582 patients with chronic hepatitis C genotype 1, 214 with fibrosis F2, and 368 with F3/F4 (F3: 148; F4: 220). RESULTS: The mean patient age was 55 years, 67% male. Type of prior response was 22% naïve, 57% relapsers, and 21% partial/null responders, 69% had high viral load (> 800,000 IU/mL). HCV genotypes were 1a (19%), 1b (69%), and 1 (12%), respectively. Sixty-five percent were non-CC IL28B genotype. Week-12 sustained virologic response (SVR12) was significantly higher among F2-naïve patients (78%) compared with F3/F4-naïve patients (60%; p = 0.039) and among F2 non-responders (67%) compared with F3/F4 non-responders (42%; p = 0.014). SVR12 among relapsers was remarkably high in both groups (F2:89% vs. F3/F4:78%). Severe anemia and thrombocytopenia were more frequent among patients with F3/F4 than those with F2 (p < 0.01). Overall, 132 patients (22%) discontinued treatment: 58 due to adverse effects, 42 due to the stopping-rule, and 32 due to breakthrough. Premature discontinuation was more frequent among patients with F3/F4 (p = 0.028), especially due to breakthrough (p < 0.001). CONCLUSIONS: This multicenter study demonstrates high efficacy and an acceptable safety profile with regard to TBT in F2-patients in clinical practice.

Management of occult hepatitis B virus infection: an update for the clinician.

Occult hepatitis B virus (HBV) infection (OBI) is defined by the presence of HBV DNA in the liver tissue of individuals who test negative for hepatitis B surface antigen (HBsAg). Patients who have recovered from acute hepatitis B can carry HBV genomes for a long time and show histological patterns of mild necro-inflammation, even fibrosis, years after the resolution of acute hepatitis, without showing any clinical or biochemical evidence of liver disease. At least in conditions of immunocompetence, OBI is inoffensive itself, but when other relevant causes of liver damage are present it might make the course of the liver disease worse. The risk of HBV transmission through transfusion is related to blood donations negative for HBsAg that have been collected during the pre-seroconversion period or during chronic OBI. Use of HBV nucleic acid amplification testing and multivalent anti-HBs antibodies in the HBsAg assays is recommended for detection of true and false OBI, respectively. It is not known if prior hepatitis B immunization with an optimal anti-HBs response in cases of HBV transmission through organ transplantation can effectively modulate or abort the infection. Use of antiviral agents as prophylaxis in patients with serological evidence of past HBV infection prevents reactivation of OBI after transplantation in most cases. Reactivation of OBI has been observed in other conditions that cause immunosuppression, in which antiviral therapy could be delayed until the HBV DNA or HBsAg becomes detectable. OBI might contribute to the progression of liver fibrosis and hepatocellular carcinoma development in patients with chronic liver disease.

Antihypertensive activity of angiotensin II AT1 receptor antagonists: a systematic review of studies with 24 h ambulatory blood pressure monitoring.

OBJECTIVE: To perform a systematic review of the antihypertensive activity of the angiotensin II AT1 receptor antagonists (ARB). METHODS: Studies in which blood pressure (BP) was measured using ambulatory BP monitoring for at least 24 h were collected from MEDLINE. Data for each treatment group, ARB, placebo or the drug used for its comparison were obtained from the selected studies. Only studies with a minimum of quality criteria were selected. The final study group contained 36 publications, with a total of 47 patient cohorts receiving ARB in monotherapy, 10 with placebo, 10 with amlodipine, and five with enalapril. The reduction in clinical and ambulatory BP during 24 h, day, night and the last 4-h period for each of the drugs analysed were calculated and adjusted by age, sex, number of participants and by the initial BP level. RESULTS: The global antihypertensive activity of ARB differs from that observed with amlodipine in the sense that the magnitude of the reduction in the BP values does not essentially depend on the initial BP values nor on the dose used. When only ARB were considered, the drug used was a determinant for systolic BP reduction, whereas for diastolic BP the influence was on the BP reduction and the duration of the antihypertensive activity. The dose used had a particular influence on the duration of the antihypertensive activity for both systolic and diastolic BP. CONCLUSION: Among the ARB, the influence is on duration more than on the magnitude of BP reduction. Dose, therefore, is an important factor in the duration of antihypertensive activity.

Long-term prospective study of recurrent venous thromboembolism in patients younger than 50 years.

Long-term incidence of recurrent venous thromboembolism (VTE) in patients younger than 50 years, not affected by a malignancy or chronic diseases, are poorly characterized. After the initial episode of VTE and cessation of oral anticoagulation, 98 patients, mean age 32.2+/-9.2 years were followed for a median of 117 months (range 6-165). Congenital risk factors for VTE were present in 36% of patients, acquired persistent (positive antiphospholipid antibodies during the whole follow-up) in 19%, and acquired transitory in 44%. Thirty episodes of recurrent VTE were documented. The cumulative incidence of VTE after 1 year of follow-up was 5.1%, 9.8% after 2 years, 14% after 4 years, and 34.2% after 8 years. In the univariate analysis, the relative risk of recurrent VTE was 2.66 [95% confidence interval (CI) 1.03-6.90] for congenital risk factors, 4.97 (95% CI 1.75-14.0) for persistent acquired (antiphospholipid antibodies), 2.64 (95% CI 1.23-5.66) for male gender and 2.27(1.00-5.15) for body mass index>30 kg/m2. In the multivariate analysis, male gender [hazard ratio (HR) 4.23, 95% CI 1.88-9.77) the presence of congenital factors (HR 3.28, 95% CI 1.25-8.63) and acquired persistent factors (HR 8.50, 95% CI 2.84-25.50) were independent risk factors for recurrent VTE. In patients under 50 years of age without malignancy or underlying chronic disease, hospitalized for an acute thromboembolic event, the presence of antiphospholipid antibodies, congenital defects of coagulation, male sex, and obesity were risk factors for recurrent VTE. These data raise the possibility that selected patients with VTE may require prolonged anticoagulation to prevent recurrent disease.

[Risk factors and clinical characteristics of thromboembolic venous disease in young patients: a prospective study]. / Estudio prospectivo de los factores de riesgo y las características clínicas de la enfermedad tromboembólica en pacientes jóvenes.

BACKGROUND AND OBJECTIVE: We aimed to determine the risk factors of thromboembolic disease in young patients and to study the clinical characteristics according to the etiology. PATIENTS AND METHOD: A prospective study of 100 patients under 50 years who were not affected by neoplasias or chronic diseases and who required hospitalization due to thromboembolic disease. The morphological diagnosis was performed by eco-Doppler, flebography, lung gammagraphy or CT scan. Risk factors assessed were antithrombin, protein C and S deficiency, presence of factor V Leiden, prothrombin G20210A, hyperhomocisteinemia, increased PAI-I, increased factor VIII, and presence of antiphospholipid antibodies (APAs). Acquired factors were also evaluated. RESULTS: In 87% of patients, a venous thrombosis was observed in lower limbs. 37% of patients had congenital risk factors and 19% had APAs, whereas in the remaining patients only acquired factors were demonstrated. Most frequent congenital factors were factor V Leiden, pothrombin G20210A, and protein C and S deficiency. Most patients presented several risk factors. A family thrombotic history was significantly more frequent in the group with congenital risk factors. CONCLUSIONS: In 56% of young patients with thromboembolic disease, a congenital etiology or APAs are identified. In these patients the number of acquired factors needed to trigger thrombosis is fewer than in patients in whom a cause is not identified.

[Renal involvement in the human immunodeficiency virus infection]. / Alteración renal en la infección por el virus de la inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: Although renal pathologies are becoming an emergent problem in the population infected by the human immunodeficiency virus (HIV), there is very scarce information about the natural course of this problem. The objective of the present study is to describe renal lesions in an autopsy series of HIV-infected patients never treated with antiretroviral therapies. PATIENTS AND METHOD: Autopsy information has been retrospectively retrieved from 61 HIV-infected subjects (mean age, 36,9 [8,4] years; 58,6% drug abusers, 84% males) died in our hospital between 1984 and 1997. None of the patients received antiretroviral therapy. All autopsy and clinical reports were considered, as well as basic analytical parameters about renal function. Renal autopsy samples were specifically reviewed. RESULTS: At the time of the last admission, 9.8% of patients had renal insufficiency, who made up 44.3% of patients having renal insufficiency anytime. Infections were the main cause of death (76%). The majority of patients (93.4%) showed histopathological renal abnormalities, which were highly heterogeneous. Renal lesions were mainly located on the tubules (96.7%) and the interstitium (60.7%). Moreover, glomeruli were affected in 55.7% of patients. Most frequent histopathological diagnosis was acute tubular necrosis (16.4%) and septic nephritic abscesses (16.4%), followed by tubulointerstitial nephritis (9%). HIV-associated nephropathy was present in two patients (3.3%). There were no significant differences when considering the existent of renal failure. CONCLUSIONS: Renal histological abnormalities are frequent in the natural evolution of HIV infection. There is an important heterogeneity of lesions, mainly involving tubules, interstitium and mesangium. The cause of renal lesions is predominantly septic, according to the chief systemic process. It does not exist any relationship between renal analytical parameters and the presence of renal damage.

Reversible posterior leukoencephalopathy secondary to indinavir-induced hypertensive crisis: a case report.

Reversible posterior leukoencephalopathy syndrome (RPLS) is an uncommon entity related to multiple and different pathologies, the most common being hypertensive crisis. It is believed to be secondary to the breakdown on the blood-brain barrier. At the beginning, it is undistinguishable from other leukoencephalopathies. However, the disappearance of brain lesions after removal of the potential cause, establish the differential diagnosis with other leukoencephalopathies. We present the case of an HIV-infected patient with a RPLS related to a hypertensive crisis short after the initiation of indinavir-containing highly active antiretroviral therapy. Once blood pressure was controlled and indinavir replaced by nelfinavir, white matter lesions at magnetic resonance imaging disappeared. The clinical and radiologic evolution excludes other diagnosis as progressive multifocal leukoencephalopathy and points indinavir as a potential hypertension-inducing agent in HIV-infected predisposed subjects.

Angina de pecho en relación con la toma de dipiridamol oral / Angina pectoris induced by oral dipyridamol

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