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Biomedical subjects

M Navasa

Publications and source records attributed to M Navasa.

At least 37 records · Page 2Linked to original sources

Hepatopulmonary syndrome in candidates for liver transplantation.

BACKGROUND: Hepatopulmonary syndrome (HPS) has been defined as a clinical triad, including chronic liver disease, gas exchange defects (increased alveolar-arterial PO2 difference irrespective of the presence of arterial hypoxemia), and widespread intrapulmonary vascular dilatations. We determined the incidence and the clinical and pulmonary functional characteristics of HPS in candidates for orthotopic liver transplantation (OLT) and tested their predicted accuracy. METHODS: We studied 80 patients with cirrhosis prospectively, and carried out contrast-enhanced (CE) echocardiography and lung function tests, including ventilation-perfusion (V(A)/Q) distributions. RESULTS: Fourteen patients had HPS (incidence, 17.5%). Patients with HPS (49 +/- 12 (+/-SD) years) had more cutaneous spiders, finger clubbing and dyspnea (P < 0.05 each) and a lower diffusing capacity (DLCO, 56 +/- 18% predicted; P < 0.001) than non-HPS patients (n = 66). Mild to moderate V(A)/Q inequalities and increased intrapulmonary shunt were predominant in HPS patients, but oxygen diffusion impairment was observed in those with hypoxemia (n = 8) only. The DLCO showed a considerable area under the receiver operating characteristic curve (0.89). CONCLUSIONS: HPS in cirrhotic patient candidates for OLT shows a high incidence and these patients present with distinctive clinical and functional features compared with non-HPS individuals. The presence of a low DLCO may be of help for the diagnosis of HPS.

Adult↗

[Hepatocellular carcinoma in a patient with hereditary hemochromatosis without cirrhosis].

Hepatocellular carcinoma in patients with hereditary hemochromatosis in the cirrhotic phase is one of the complications causing greatest mortality and may present in spite of removal of excess iron by bloodletting. Hepatocellular carcinoma is usually considered to occur in cirrhotic livers and consequently measures for the early diagnosis of this complication are only recommended in this type of patient. We present the case of a 69-year-old female patient with non-cirrhotic hemochromatosis who, 6 years after undergoing successful treatment, developed hepatocellular carcinoma. This observation should be added to the 12 cases published in the literature. Criteria should be established for the early diagnosis of hepatocellular carcinoma in patients with hereditary hemochromatosis, irrespective of whether they have cirrhosis.

Aged↗

[Infectious complications associated with liver transplantation: analysis of 104 patients].

OBJECTIVE: Infectious complications are the main cause of morbidity and mortality during the first year after liver transplantation. The aim of the present study was to determine the incidence, microorganisms and factors associated with the development of infectious complications. PATIENTS AND METHOD: Retrospective analysis of infectious episodes during the first year after transplantation in 104 patients undergoing transplantation between April 1995 and December 1996. The various clinical variables related to the pre-transplant disease, the surgical intervention and post-transplant evolution were evaluated with the aim of identifying predictive factors for the development of bacterial infectious complications. RESULTS: During the first year, 51 patients (49%) presented 111 infectious episodes. The most frequent infections were bacterial (66%); 21% were cytomegalovirus infections and 22% were fungal. The incidence of bacterial infections was highest during the first month (80% of all infectious episodes in this period). Two variables were independently associated with the development of bacterial infections in the first month following transplantation: prolonged ischemia of the graft (p = 0.002) and length of stay in the intensive care unit (p = 0.002). Infectious complications caused 8 of the 11 deaths that occurred during the 1-year follow-up. Mortality associated with invasive fungal infections was 100%. CONCLUSIONS: Although the overall incidence of infections and associated mortality has decreased, it remains the main cause of mortality and morbidity in the first year after transplantation.

Female↗

Increased production of vascular endothelial growth factor in peritoneal macrophages of cirrhotic patients with spontaneous bacterial peritonitis.

Spontaneous bacterial peritonitis (SBP) is a common complication of cirrhotic patients with ascites that usually results in renal failure and death despite the efficacy of the current antibiotic therapy. The pathogenesis of these phenomena is poorly known but it has been related to the production of vasoactive cell mediators locally acting on the splanchnic vasculature. Because previous studies showed that peritoneal macrophages of cirrhotic patients may produce high quantities of vascular endothelial growth factor (VEGF), a powerful vessel permeabilizing agent, when stimulated by cytokines and bacterial lipopolysaccharide, the present study was aimed to seek whether peritoneal macrophages of SBP patients are induced to produce increased amounts of VEGF. Our results indicate that the production rate and the messenger RNA (mRNA) and protein expression of this substance are increased in macrophages of patients with SBP in comparison with those of noninfected cirrhotic patients. This characteristic feature is absent in circulating monocytes of these patients. Moreover, enhanced endothelial cell proliferation induced by conditioned medium of macrophages isolated from the ascites of patients with SBP is abolished by anti-VEGF antibody, and peritoneal tissue of cirrhotic patients expresses both VEGF receptors, Flt-1 and KDR. These results, therefore, are consistent with the concept that locally released macrophage-derived VEGF may result in increased vascular permeability and plasma leakage in the peritoneal vessels of cirrhotic patients with SBP.

Bacterial Infections↗

Hepatitis B immunoglobulin discontinuation followed by hepatitis B virus vaccination: A new strategy in the prophylaxis of hepatitis B virus recurrence after liver transplantation.

It is widely agreed that hepatitis B virus immunoglobulin (HBIG) should be administered for at least 12 months to patients transplanted for hepatitis B virus (HBV)-related diseases to prevent HBV recurrence. No data are available, however, on how long this treatment should be used, and most centers currently administer HBIG on a life-long basis. Herein, we report the results of a new prophylactic strategy aiming at the discontinuation of HBIG treatment and consisting of the administration of double dose recombinant HBV vaccine (0, 1-, and 6-month schedule) to liver transplant recipients fulfilling the following criteria: (1) liver transplantation for conditions related to nonreplicative HBV infection (hepatitis B surface antigen [HBsAg] positive, hepatitis B e antigen [HBeAg] negative, and HBV DNA negative); (2) at least 18 months of HBIG administration; and (3) no HBV infection recurrence, normal or slightly altered liver graft function, and low-grade immunosuppression at the time of vaccination. Seventeen patients received HBV vaccination and 14 of them (82%) developed protective serum titers of anti-HBs (>10 IU/L). Six patients seroconverted after a first course of vaccination, whereas 8 patients required a second course (3 additional doses of vaccine). Responding patients were followed for a median of 14 months (range, 3-50) after seroconversion. During this period no HBV recurrence occurred and in only 2 patients a decrease of anti-HBs titers below 10 UI/L was observed. Our data suggest that in selected liver transplant recipients, posttransplantation HBV vaccination may be a useful and cost-effective strategy in the prophylaxis of HBV recurrence, allowing the discontinuation of life-long HBIG treatment.

Adult↗

Ascites after liver transplantation.

Massive ascites after liver transplantation, although uncommon, usually represents a serious adverse event. The pathogenesis of this complication has not been adequately investigated. To determine the incidence, characteristics, and pathogenic factors of massive ascites after liver transplantation (ascitic fluid > 500 mL/d for >10 days), the charts of 378 liver transplant recipients were reviewed. Massive ascites occurred in 25 patients (7%). Mean ascitic fluid production was 960 mL/d (range, 625 to 2,350 mL/d), and the duration of ascites was 77 days (range, 15 to 223 days). The ascitic fluid had a high protein content (36 +/- 7 g/L; range, 25 to 50 g/L). When patients who did and did not develop massive ascites were compared, significant differences were found in receptor sex (men, 88% v 60%, respectively; P <.01) and surgical technique (inferior vena cava preservation with piggyback technique, 72% v 41%; P <.01). Significantly increased wedged and free hepatic venous pressures and gradients between hepatic vein and right atrial pressures were found in patients who developed ascites, suggesting a difficulty in graft blood outflow. Massive ascites was associated with renal impairment, increased incidence of abdominal infection, prolonged hospitalization, and a tendency toward reduced survival. In conclusion, massive ascites after liver transplantation is relatively uncommon but associated with increased morbidity and mortality and is predominantly related to difficulties of hepatic venous drainage. Measurement of hepatic vein and atrial pressures to detect a significant gradient and correct possible alterations in hepatic vein outflow should be the first approach in the management of these patients.

Adult↗

Terlipressin plus albumin infusion: an effective and safe therapy of hepatorenal syndrome.

BACKGROUND/AIM: Ornipressin, a vasopressin analog with potent splanchnic vasoconstrictor action, has been shown to reverse hepatorenal syndrome. However, its usefulness in clinical practice is limited by frequent ischemic complications. The aim of this study was to assess the efficacy of terlipressin, an analog of vasopressin with a low profile of side effects, plus albumin in this condition. METHODS: Nine consecutive patients with cirrhosis and hepatorenal syndrome were included in a pilot study of terlipressin (0.5-2 mg/4 h i.v.) therapy associated with iv albumin. RESULTS: Treatment (9 days, range 5-15) was associated with a marked reduction of serum creatinine (3.9+/-0.7 to 1.3+/-0.1 mg/dl, p<0.001, mean+/-SE). Reversal of hepatorenal syndrome (reduction of creatinine below 1.5 mg/dl) was observed in seven of the nine patients. There was a remarkable improvement in circulatory function, with an increase in mean arterial pressure (68+/-2 to 80+/-4 mmHg, p<0.05) and suppression of vasoconstrictor systems activity (plasma renin activity and plasma norepinephrine decreased from 23+/-12 ng/ml x h and 1549+/-373 pg/ml to 3.5+/-2 ng/ml x h and 373+/-98 pg/ml, respectively, p<0.01 for both). No patient developed signs of intestinal, myocardial or distal ischemia. CONCLUSIONS: Terlipressin associated with albumin appears to be a safe and effective treatment of hepatorenal syndrome.

Adult↗

Prevalence and prognostic value of hepatocellular carcinoma in cirrhotic patients presenting with spontaneous bacterial peritonitis.

BACKGROUND/AIMS: This study examined the prognostic power of hepatocellular carcinoma in patients presenting an episode of spontaneous bacterial peritonitis treated with 3rd generation cephalosporins or quinolones, and subsequent prophylaxis with norfloxacin until death or transplantation. METHODS: The study comprises the prospective evaluation of 168 consecutive cirrhosis patients presenting an episode of spontaneous bacterial peritonitis. RESULTS: Hepatocellular carcinoma was diagnosed in 35 out of the 168 (20%) patients included in the study (10 single; 25 advanced tumors). Renal impairment developed in 82 patients. Resolution of infection was achieved in 90% of the cases, the hospital survival being 70%. Renal impairment, advanced tumor stage, albumin, and GGT showed independent prognostic value for hospital mortality. At the end of follow-up 101 patients had died, the 1- and 2-year survival being 36% and 31%, respectively. Four variables independently predicted survival: advanced tumor (OR: 3.9; p=0.00001), renal impairment (OR: 2.1; p=0.00001), bilirubin (OR: 1.6; p=0.02) and creatinine (OR: 1.3; p=0.03). Advanced tumor retained independent predictability in patients surviving hospitalization (OR: 7.5; p=0.0001), the 6-month survival being significantly lower in patients with advanced tumor (12% vs 57%, p<0.00001). CONCLUSION: The prevalence of hepatocellular carcinoma in cirrhotic patients with spontaneous bacterial peritonitis is high, and its presence should be actively sought. Advanced tumor impairs both hospital and long-term survival, and should be considered in the design of future trials.

Aged↗

Diagnosis, treatment and prevention of spontaneous bacterial peritonitis.

Spontaneous bacterial peritonitis (SBP) is a frequent complication in cirrhotic patients with ascites. Diagnosis of SBP is established by a polymorphonuclear cell count in ascitic fluid > or =250 cells/mm(3). The organism responsible for the infection is isolated in 60-70% of the cases. The remaining cases are considered to have a variant of SBP (culture-negative SBP) and are treated in the same way as those with a positive culture. The SBP resolution rate ranges between 70 and 90%, and hospital survival between 50 and 70%. An early diagnosis and the use of a more adequate antibiotic therapy are the most probable reasons for the improvement in prognosis for SBP in recent decades. Despite the resolution of the infection, SBP may trigger severe complications such as renal impairment, gastrointestinal bleeding and accentuation of hepatic insufficiency which are responsible for the associated mortality. Patients recovering from an episode of SBP should be considered as potential candidates for liver transplantation.

Anti-Bacterial Agents↗

Liver transplantation and quality of life.

To date, more than 50,000 liver transplantations have been performed around the world; the survival rate five years after transplantation ranges from 60% to 65%. One of the fundamental objectives for liver transplantation teams is to achieve the best possible quality of life (QOL) for the patients. A concise analysis of the methodology used (15 questionnaires) to measure QOL of patients with liver transplants is described. The authors suggest that now is the time to establish a database so that a validated instrument will be available to compare QOL results from all the liver transplantation programs. Liver transplantation is believed to improve QOL, although there are several problems with some of the papers published on this subject. Some studies are retrospective, whereas in others, patients in bad physical conditions are excluded from the study; in quite a few prospective studies, deaths are not included in the data analysis. Finally, the authors provide a brief, concise analysis of late complications and of recurrence of the disease after liver transplantation, which influence QOL.

Health Status Indicators↗

[Autoimmune hepatitis associated with thyroiditis and hypophysitis. A case report].

Autoimmune hepatitis primarily affects women and 40% of cases are associated with extrahepatic autoimmune dysfunction. Thyroiditis, ulcerative colitis and rheumatoid arthritis are the most commonly implicated entities. We present a 46-year-old woman with type-II autoimmune hepatitis and Graves disease who presented deterioration in level of consciousness, her symptoms mimicking severe liver failure. Hormone studies and nuclear magnetic resonance imaging revealed hypophysitis, which led to hypothyroidism and metabolic encephalopathy. The syndrome was resolved with hormone replacement therapy.

Diagnosis, Differential↗

Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis.

BACKGROUND: In patients with cirrhosis and spontaneous bacterial peritonitis, renal function frequently becomes impaired. This impairment is probably related to a reduction in effective arterial blood volume and is associated with a high mortality rate. We conducted a study to determine whether plasma volume expansion with intravenous albumin prevents renal impairment and reduces mortality in these patients. METHODS: We randomly assigned 126 patients with cirrhosis and spontaneous bacterial peritonitis to treatment with intravenous cefotaxime (63 patients) or cefotaxime and intravenous albumin (63 patients). Cefotaxime was given daily in dosages that varied according to the serum creatinine level, and albumin was given at a dose of 1.5 g per kilogram of body weight at the time of diagnosis, followed by 1 g per kilogram on day 3. Renal impairment was defined as nonreversible deterioration of renal function during hospitalization. RESULTS: The infection resolved in 59 patients in the cefotaxime group (94 percent) and 62 in the cefotaxime-plus-albumin group (98 percent) (P=0.36). Renal impairment developed in 21 patients in the cefotaxime group (33 percent) and 6 in the cefotaxime-plus-albumin group (10 percent) (P=0.002). Eighteen patients (29 percent) in the cefotaxime group died in the hospital, as compared with 6 (10 percent) in the cefotaxime-plus-albumin group (P=0.01); at three months, the mortality rates were 41 percent (a total of 26 deaths) and 22 percent (a total of 14 deaths), respectively (P=0.03). Patients treated with cefotaxime had higher levels of plasma renin activity than those treated with cefotaxime and albumin; patients with renal impairment had the highest values. CONCLUSIONS: In patients with cirrhosis and spontaneous bacterial peritonitis, treatment with intravenous albumin in addition to an antibiotic reduces the incidence of renal impairment and death in comparison with treatment with an antibiotic alone.

Adult↗

Vascular endothelial growth factor production in peritoneal macrophages of cirrhotic patients: regulation by cytokines and bacterial lipopolysaccharide.

Vascular endothelial growth factor (VEGF) is an angiogenic peptide with vascular permeability and relaxing properties. This study assessed whether peritoneal macrophages of cirrhotic patients can be up-regulated to produce VEGF under proper stimulatory conditions. Macrophages were isolated from ascites. VEGF protein secretion and mRNA expression were measured in basal conditions and after stimulation with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), and interleukin-1 (IL-1). These substances induced a time- and dose-dependent increase in both VEGF production and transcript expression. Assays with actinomycin D showed that VEGF mRNA induction is secondary to both higher VEGF gene transcription and mRNA stability. Ascites and plasma concentration of VEGF was also measured in cirrhotic patients with (n = 15) and without (n = 10) spontaneous bacterial peritonitis (SBP). Plasma values did not differ between both groups of patients. However, ascites VEGF levels were higher in SBP patients than in noninfected cirrhotic patients (710 +/- 183 vs. 94 +/- 15 pg/mL; P <.025). These results indicate that cytokines and LPS markedly increase VEGF protein secretion and mRNA expression in macrophages of cirrhotic patients, and suggest that this substance could be an important mediator of the pronounced arterial vasodilation frequently occurring in SBP patients.

Ascites↗

Nitric oxide production and inducible nitric oxide synthase expression in peritoneal macrophages of cirrhotic patients.

The present study assessed whether peritoneal macrophages isolated from cirrhotic patients produce nitric oxide (NO) and express NO synthase type II (NOS II) mRNA and protein. Patients with cirrhosis and ascites without peritonitis or with unresolved or resolved spontaneous bacterial peritonitis (SBP) were studied. Following paracentesis, ascites NO(2)(-) + NO(3)(-) content (NOx) was measured. Peritoneal macrophages from ascites were seeded on well plates, and NO(2)(-) in the medium was determined. NOx was higher in patients with unresolved or resolved SBP than in cirrhotic patients without peritonitis. Macrophages of patients with SBP or resolved SBP produced NO(2)(-) after 30 hours in culture, but those obtained from patients without peritonitis did not. Reverse-transcription polymerase chain reaction (RT-PCR) and immunocytochemical analysis revealed the presence of a clear signal for NOS II mRNA and protein in macrophages of SBP patients, regardless of whether or not the infection subsided. Therefore, peritoneal macrophages isolated from cirrhotic patients with unresolved or resolved SBP produce NO and express the NOS II mRNA and protein, suggesting that NOS II may contribute to the control of SBP, or to its associated pathology, in human cirrhosis.

Adult↗