Biomedical subjects

Magdalena Salcedo

Publications and source records attributed to Magdalena Salcedo.

8 recordsLinked to original sources

PubMed2006

Does interferon improve portal hypertension?

Chronic hepatitis C is the leading cause of advanced liver disease in the Western world. Most patients with liver cirrhosis develop portal hypertension (PHT) (i.e. an abnormal gradient between portal and inferior vena cava pressures), responsible for the most frequent and severe complications of liver disease and, as a consequence, the main cause of death and liver transplantation in those patients. The existence of a potential beneficial effect of antiviral therapy (AVT) on liver inflammation and fibrosis, partially independent of the degree of virological response, has been recently reported. However, the possible influence of these histological changes on PHT has not been evaluated. In this article, we summarize the available findings regarding the effect of AVT on PHT in patients with advanced chronic hepatitis C, as well as its possible implications for clinical practice and future avenues of investigation.

Antiviral Agents↗

PubMed2006

Antiviral therapy decreases hepatic venous pressure gradient in patients with chronic hepatitis C and advanced fibrosis.

BACKGROUND: Antiviral therapy (AVT) may improve liver histology in patients with advanced viral hepatitis but its effect on portal pressure remains unknown. AIM: This study was aimed to evaluate the influence of antiviral therapy (AVT) on hepatic venous pressure gradient (HVPG) in hepatitis C virus infected patients with portal hypertension. METHODS: Twenty compensated patients with chronic hepatitis C, fibrosis stage 3 or 4 and HVPG > 5 mmHg received PEG-IFN alpha2b plus ribavirin. Every patient underwent liver biopsy and portal pressure measurements before and immediately after AT. Biopsies were evaluated according to METAVIR score. RESULTS: HVPG significantly dropped in all but one treated patient, with a mean (SD) reduction of 28.2 (12)%[13.8 (5.6) Vs. 10.2 (3.8) mmHg, p = 0.005]. The percentage of HVPG decrease was significantly greater in patients who achieved a virological end of treatment response [26.2 (12.5)% Vs. 12.7 (8.5)%, p = 0.05] and in those with a decrease of at least 2 points in the grade of inflammation [35.7 (4.5)% Vs. 22.1 (9.5)%, p = 0.015]. Nine out of 11 patients with baseline HVPG > or = 12 mmHg showed a decrease greater than 20% (3/11) or under the 12 mmHg threshold (6/11). CONCLUSIONS: AVT reduces HVPG in compensated patients with advanced hepatitis C (fibrosis stage 3 or 4) and portal hypertension.

Adult↗

PubMed2005

Influence of hepatic venous pressure gradient on the prediction of survival of patients with cirrhosis in the MELD Era.

Measurements of portal pressure, usually obtained via the hepatic venous pressure gradient (HVPG) may be a prognostic marker in cirrhosis. The aim of this study was to evaluate the impact of HVPG on survival in patients with cirrhosis in addition to the Model for End-Stage Liver Disease (MELD) score. We also examined whether inclusion of HVPG in a model with MELD variables improves its prognostic ability. Retrospective analyses of all patients who had HVPG measurements between January 1998 and December 2002 were considered. Proportional hazards Cox models were developed. Prognostic calibrative and discriminative ability of the model was evaluated. In this period, 693 patients had a hepatic hemodynamic study, and 393 patients were included. Survival was significantly worse in those patients with greater HVPG value (univariate HR, 1.05; 95% CI, 1.02-1.08; P = .001). HVPG remained as an independent variable in a model adjusted by MELD, ascites, encephalopathy, and age (multivariate HR, 1.03; 95% CI, 1.00-1.06; P = .05) so that each 1-mmHg increase in HVPG had a 3% increase in death risk. In addition, HVPG as well as MELD score variables and age, significantly contributes to the calibrative predictive capacity of the prognostic model; however, discriminative ability improved only slightly (overall C statistic [95% CI]; MELD score variables: 0.71 [0.62-0.80], MELD score variables, age, and HVPG 0.76: [0.69-0.83]). In conclusion, HVPG has an independent effect on survival in addition to the MELD score. Although inclusion of HVPG and age in a survival predicting model would improve the calibrative ability of MELD, its discriminative ability is not significantly improved.

Adult↗

PubMed2004

[Liver transplantation in patients with HIV infection: a reality in 2004].

According to current estimates, there are 60,000 to 80,000 HIV and HCV coinfected individuals in Spain, and 5,000 to 10,000 HIV and HBV coinfected individuals. Among these patients, 10% to 15% have liver cirrhosis. Thus, end-stage liver disease is one of the major causes of death in our country. Liver transplantation is the only therapeutic option for these patients. Accumulated experience in North America and Europe in the last five years indicates that three-year survival in HIV-positive liver transplant recipients is similar to that of HIV-negative recipients. The selection criteria for HIV transplant candidates includes the following: no history of opportunistic infections, CD4 lymphocyte count higher than 100 cells/mm3, and HIV viral load suppressible with antiretroviral treatment. In Spain, where the majority of patients are former drug abusers, complete abstinence from heroin or cocaine use during two years is also required, with the possibility of the patient being in a methadone program. To date 26 hepatic transplants have been performed in the same number of patients, with only two deaths (7%) after a median follow-up of eight months (1-28). The main problems in the post-transplantation period in all the series has been recurrent HCV infection, which is the principle cause of post-transplantation mortality, and pharmacokinetic and pharmacodynamic interactions between the antiretroviral and immunosuppressive agents. There is little experience with pegylated interferon and ribavirin treatment in this population.

Anti-HIV Agents↗

PubMed2003

Hepatic and systemic haemodynamic changes after MARS in patients with acute on chronic liver failure.

Hyperdynamic circulation and portal hypertension characterize acute on chronic liver failure (AoCLF), partially because of circulating mediators. Molecular Absorbents Recirculating System (MARS) may remove some of these substances. The objective of this study was to evaluate the effect of MARS on portal pressure, systemic haemodynamic and endogenous vasoactive systems. MARS treatment was performed in four patients with AoCLF (mean age 36.2 +/- 3.1 years; Child-Pugh C 11 +/- 1.8 points; three AAH and one NASH). Systemic and splanchnic haemodynamic measurements were performed before and after each session. Plasmatic renin activity (PRA) and NE were measured at baseline, at the end of the sessions and 10 days after MARS. All patients had severe portal hypertension (HVPG=23 +/- 7 mmHg) and pronounced hyperdynamic circulation (MAP 77.8 +/- 11.7 mmHg; CO 11.2 +/- 1.6 L/min; SVRI 478.5 +/- 105 dyne s/cm5). HVPG decreased at the end of the first session in all patients (23 +/- 7 mmHg vs 17.3 +/- 9.9 mmHg; P=0.05; mean decrease 32 +/- 24%) because of a decrease in WHVP (40.7 +/- 5.6 mmHg vs 34 +/- 9.6 mmHg; P=0.025; mean decrease 18 +/- 19%). MARS significantly attenuated hyperdynamic circulation as shown by a decrease in CO (11.2 +/- 1.6 L/min vs 9.4 +/- 2.1 L/min; mean decrease 12.3%), with an increase in MAP (77.8 +/- 11.7 mmHg vs 84.2 +/- 8 mmHg; mean increase 9.2%) and in SVRI (478.5 +/- 105 dyne s/cm5 vs 622 +/- 198 dyne s/cm5; mean increase 41%). PRA and NE decreased significantly (14.2 +/- 17.2 ng/mL/h vs 3.7 +/- 3.4 ng/mL/h; 1319 +/- 1002 pg/mL vs 617 +/- 260 pg/mL, respectively). The NE decrease was correlated to HVPG decrease (r=1, P=0.01). MARS decreases portal hypertension and ameliorates hyperdynamic circulation in patients with AoCLF, probably mediated by clearance of vasoactive substances. Further studies are necessary to confirm these results.

Adult↗

PubMed2002

Response to steroids in de novo autoimmune hepatitis after liver transplantation.

Graft dysfunction associated with autoimmune phenomena has been recently described in liver transplant recipients without previous autoimmune disease. However, the natural history, diagnostic criteria, and definitive therapeutic approach of de novo autoimmune hepatitis (de novo AIH) are poorly understood. We report 12 cases of de novo AIH 27.9 +/- 24.5 months after liver transplantation: the outcome of 7 patients treated with steroids is compared with a group of 5 nontreated patients. Nontreated patients lost the graft after 5.8 +/- 2.6 months from de novo AIH onset. All treated patients were alive after 48.4 +/- 14 (29-65) months from de novo AIH onset, and none of them lost the graft. However, 5 patients relapsed in relation to steroid tapering. All patients presented an atypical antiliver/kidney cytosolic autoantibody, associated to classical autoantibodies in 10 cases. Histological study showed several degrees of lobular necrosis and inflammatory infiltrate. HLA antigen frequencies and matching were compared with 2 control groups (16 orthotopic liver transplantation [LTX] patients without de novo AIH and 929 healthy blood donors); de novo AIH patients showed a higher prevalence of HLA-DR3 (54.5% vs. 25.9%, P =.04) than healthy controls, which was not observed in LTX patients without de novo AIH. In conclusion, this new disease should be included in the differential diagnosis of unexplained graft dysfunction. In addition, treatment with steroids results in a dramatically improved outcome. However, maintenance therapy is usually required.

Adult↗

PubMed2002

Endoscopic treatment versus endoscopic plus pharmacologic treatment for acute variceal bleeding: a meta-analysis.

Endoscopic therapy, involving either injection sclerosis or band ligation, is considered the intervention of first choice for acute variceal bleeding (AVB). Pharmacologic agents have also been shown to be highly effective in the control of the bleeding episode. The purpose of this meta-analysis was to assess whether vasoactive drugs may improve the efficacy of endoscopic therapy (injection sclerosis or band ligation) in the control of AVB and thus increase survival rates. Computer databases and scientific meeting abstracts from 1994 to 2001 were used to search for randomized trials that compared the combined use of endoscopic and drug therapy with endoscopic therapy alone in the control of AVB. Eight trials involving 939 patients fulfilled the selection criteria and the following evaluated by standard meta-analysis methods: initial hemostasis, 5-day hemostasis, 5-day mortality, and adverse events. Combined treatment improved initial control of bleeding (relative risk [RR], 1.12; 95% confidence interval (CI), 1.02-1.23), and 5-day hemostasis (RR, 1.28; 95% CI, 1.18-1.39), with numbers of patients needed to treat (NNT) of 8 and 5, respectively. The difference in favor of combined treatment remained significant when trials that used drugs other than octreotide or that included a low proportion of alcoholic patients (<40%) or high-risk cirrhotic patients (<35%) were excluded. Mortality was not significantly decreased by combined therapy (RR, 0.73; 95% CI, 0.45-1.18). Severe adverse events were similar in both groups. In conclusion, in patients with AVB, pharmacologic agents improve the efficacy of endoscopic therapy to achieve initial control of bleeding and 5-day hemostasis, yet fail to affect mortality.

Acute Disease↗

PubMed2002

Granulocyte colony-stimulating factor improves deficient in vitro neutrophil transendothelial migration in patients with advanced liver disease.

Bacterial infections are frequent complications in patients with liver cirrhosis. Cirrhotic patients present abnormalities in both innate and adaptive immune responses, including a deficient neutrophil recruitment to infected sites. The purpose of this study was to assess neutrophil-endothelium interactions in cirrhotic patients and evaluate the effects of G-CSF on this process. We studied neutrophil adhesion and transendothelial migration in 14 cirrhotic patients and 14 healthy controls. We also analyzed neutrophil expression of the adhesion molecules CD62L and CD11b in whole blood by flow cytometry. Cirrhotic patients expressed higher levels of CD11b than healthy controls, whereas CD62L expression was significantly lower, suggesting exposure of neutrophils to activating agents within the bloodstream. Neutrophils from cirrhotic patients showed increased adhesion to both resting and tumor necrosis factor alpha-stimulated microvascular endothelial cells and decreased transendothelial migration. Granulocyte colony-stimulating factor (G-CSF) (100 ng/ml) significantly enhanced neutrophil adhesion to microvascular endothelial cells in healthy controls but not in cirrhotic patients. G-CSF also significantly improved neutrophil transmigration in cirrhotic patients and healthy controls. In conclusion, cirrhotic patients exhibit increased neutrophil adhesion to microvascular endothelium and deficient transendothelial migration. G-CSF enhances neutrophil transendothelial migration in cirrhotic patients despite having no effect on neutrophil adhesion. Therefore, G-CSF may be able to increase neutrophil recruitment into infected sites in these patients.

Adult↗