Epidemiology, clinical characteristics, and outcome of invasive aspergillosis in renal transplant patients.

BACKGROUND: Invasive aspergillosis (IA) has been considered an infrequent complication after renal transplantation. We aimed to evaluate the differences in clinical and epidemiologic characteristics of IA between renal and other types of transplantation. METHODS: We reviewed all cases of solid organ transplant (SOT) recipients from Hospital Clinic at Barcelona, who had proven and probable IA, according to the EORTC/MSG criteria, between June 2003 and December 2010. RESULTS: A total of 1762 transplants were performed. From this cohort, 27 cases of IA were diagnosed (1.5%): in 56% (15/27) liver, 33% (9/27) kidney, and 11% (3/27) combined transplant. The median onset time from renal and non-renal transplants to IA was 217 and 10 days, respectively (P < 0.001). There were 6 cases (22%) of late IA (>6 months), all in kidney recipients (P < 0.001). Renal transplant patients with IA more frequently had chronic lung disease (44% vs. 6%) and chronic heart failure (33% vs. 6%); they also had none of the classical risk factors for IA defined for liver transplantation (0% vs. 33%, P = 0.001), and therefore they did not receive antifungal prophylaxis (0% vs. 72%, P = 0.001). In 14/24 patients, serum galactomannan antigen was positive, and this related to higher mortality. CONCLUSIONS: While classical risk factors described for IA in liver recipients are still valid, IA appears later in renal patients and is commonly associated with co-morbid conditions.

Assessment of portal hypertension in humans.

Patients suspected of having portal hypertension (either by clinical history, physical examination, or previous diagnosis) should undergo ultrasonography and upper gastrointestinal endoscopy. Ultrasonography, preferably using the duplex technique, can disclose the patency of the portal venous system, the presence of signs of portal hypertension (splenomegaly, portocollateral vessels, repermeabilization of the umbilical vein, and so forth) and provide additional information about liver, biliary, or pancreatic diseases that may be the cause of portal hypertension. Endoscopy can assess the presence and size of gastroesophageal varices, the appearance of the variceal wall, and the presence and severity of portal hypertensive gastropathy. Patients showing a patent portal vein should have hepatic vein catheterization to evaluate the presence of presinusoidal, sinusoidal, or postsinusoidal portal hypertension. Patients in whom presinusoidal portal hypertension is suspected (those having esophageal varices with an HVPG below 10 mm Hg) should have liver biopsy and percutaneous transhepatic measurement of portal pressure. In sinusoidal portal hypertension, the results of endoscopy and HVPG measurement are decisive for the therapeutic management of the patients. The authors' results indicate that, before starting prophylactic therapy with beta-blockers, all patients should undergo at least an hepatic vein catheterization to assess HVPG; it would be preferable to have a variceal pressure measurement also. These measurements must be repeated 3 to 4 weeks after the final dose of therapy has been reached to assess the risk of variceal bleeding or rebleeding.

[The applicability and diagnostic effectiveness of transjugular liver biopsy]. / Aplicabilidad y rentabilidad diagnóstica de la biopsia hepática transyugular.

BACKGROUND: The aim of this study was to evaluate the applicability, the diagnostic profitability and the incidence of complications associated with tranjugular liver biopsy associated with the measurement of the hepatic venous pressure gradient (HVPG). PATIENTS AND METHODS: The clinical histories of 829 consecutive patients in whom transjugular liver biopsy was performed from 1982 to 1993 were reviewed. The diagnostic value of the sample obtained was evaluated in all the patients and the HVPG determined. Moreover, the size of the greatest fragment obtained during biopsy was also determined. RESULTS: Material for histologic study was obtained in 95% of the cases. In 70% the biopsy was diagnostic, in 11% it provided data contributing to diagnosis and in 19% it was not useful. Potentially severe complications were presented in 0.8% of cases being fatal in one (0.1%). The obtention of a fragment of small size was significantly associated with the presence of disease with marked fibrosis and high HVPG. A HVPG > 10 mmHg in patients with a suspicion of liver disease had a sensibility of 92% and a specificity of 63% for the diagnosis of hepatic cirrhosis. In 83% of patients with a GPVH > 10 mmHg in whom the biopsy was not useful, the diagnosis of hepatic cirrhosis was performed by other methods. CONCLUSIONS: Transjugular biopsy in a safe, effective diagnostic method in patients with severe coagulation disorders. The appearance of the material obtained and the HVPG provide useful information for diagnosis although the biopsy is not diagnostic.

[Isolated rectal Kaposi's sarcoma]. / Sarcoma de Kaposi de localización rectal aislada.

We report a case of isolated rectal Kaposi's Sarcoma in a homosexual man with active Human Immunodeficiency Virus infection. Although gastrointestinal tract affection is not infrequent, it is usually associated with the existence of skin lesions. A few cases of noncutaneous gastrointestinal Kaposi's Sarcoma have been described, but no one affecting only the rectum. This is a diagnostic possibility in patients with Human Immunodeficiency Virus infection and rectal symptoms.

[Effects of percutaneous intrahepatic portosystemic shunt on splanchnic and systemic hemodynamics in patients with portal hypertension]. / Efectos de la derivación portosistémica percutánea intrahepática sobre la hemodinámica esplácnica y sistémica en pacientes con hipertensión portal.

Transjugular intrahepatic portosystemic shunt (TIPS) is a calibrated shunt directed at reducing the portal pressure gradient with a low incidence of hepatic encephalopathy and deterioration of hepatocellular function. The present study investigated the effects of TIPS on splanchnic and systemic hemodynamics on liver function and on the development of encephalopathy. A group of 30 patients treated with TIPS were included in the study: 26 patients with hepatic cirrhosis for an hemorrhagic episode by esophageal varices not controlled by medical treatment and sclerotherapy and in 4 cases with the Budd-Chiari syndrome for ascites refractory to medical treatment. Before, at 24 hours and 2 months after TIPS, the portal pressure gradient, cardiopulmonary pressure and cardiac output, blood flow of the azygos vein, and hepatic clearance of indocyanine green as indexes of liver function were determined. TIPS significantly decreased the portal pressures gradient and azygos blood flow. This was associated with a significant increase in cardiac output and a significant decrease in peripheral vascular resistance and hepatic clearance of indocyanine green. Portal flow deviated by TIPS was greater in the 9 patients (30%) who developed hepatic encephalopathy during follow up. In conclusion, TIPS effectively reduces portal hypertension. Nonetheless, it is associated with an increase in hyperdynamic circulation, a high incidence of encephalopathy and a deterioration in liver function.

Limitations of use of the noninvasive clearance of indocyanine green as a prognostic indicator of graft function in liver transplantation.

AIM: To assess the prognostic value of noninvasive indocyanine green (ICG) clearance (ICG-pulse-densitometric method [PDR]) for the outcome of liver grafts after transplantation. METHODS: ICG-PDR, hepatic artery resistance index, cardiac output, transaminases, prothrombin time, bilirubin, albumin, hematocrit at 48 to 72 hours after transplantation were analyzed with reference to outcome among 59 liver graft recipients. RESULTS: Two grafts were lost at 10 and 88 days during the initial hospitalization. These two patients only differed from the other recipients in the need for packing (1/2 versus 3/57) and degree of hypoproteinemia (46 ± 0 versus 51 ± 7.8 g/L), whereas they had similar ICG-PDR values (16.7%/min and 21.8%/min versus 17.3%/min ± 7.2%/min). Seven patients showed an ICG-PDR ≤ 8.8%/min, a previously identified cutoff for early postoperative complications. These patients versus the other 52 significantly differed in prothrombin index (47.9% ± 15.9% versus 64.3% ± 11.7%, P = .001) and bilirubin (8.3 ± 3.2 versus 3.3 ± 2.9 mg/dL, P = .0001). Early postoperative complications--primary graft nonfunction, hepatic artery thrombosis, or septic shock--responsible for an ICG-PDR ≤ 8.8%/min were observed in 2/7 patients. Interestingly, six cases developed an early (range: 3-15 days) rejection episode. In all the cases rejection suspected by analytical abnormalities was confirmed by liver biopsy. Among the overall series of patients, ICG-PDR significantly correlated with serum albumin (r = 0.345; P = .007), bilirubin (r = -0.514; P = .0001), and hematocrit (r = 0.462; P = .0001) but not with transaminases, prothrombin index, cardiac output, or hepatic artery resistance index. Actuarial 72-month probability of graft survival was 75%. Overall, 14 grafts were lost over a median follow-up of 78 months (range 1-99 m). There were no significant differences among early ICG-PDR values among grafts lost vs retained upon follow-up. CONCLUSION: ICG-PDR measured once early after liver transplantation did not offer relevant information to predict individual patient outcomes in the immediate postoperative phase. This lack of prognostic value may have been due to the multiple confounding factors involved in ICG metabolism after liver transplantation.

Liver transplantation for acute liver failure: a Spanish perspective.

The Spanish characteristics of organ donation (high accessibility to a transplant) and the different proportion in the etiologies of acute liver failure (ALF), namely, the very low incidence of paracetamol overdose causing this syndrome in contrast with other Western countries, are the causes of some specific features of emergency liver transplantation for ALF. The most relevant are the short time between the need for a graft and effective urgent liver transplant, and the high proportion of patients who undergo this therapy. This paper analyzes these characteristics and provides information about the use of biological and nonbiological extracorporeal liver support devices in acute liver failure, suggesting that these systems should be tested in countries with a long waiting times for urgent liver transplantation, or in patients with ALF and contraindications for transplantation.

Autosomal dominant polycystic kidney disease with anticipation and Caroli's disease associated with a PKD1 mutation. Rapid communication.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal hereditary disorder. Clinical expression of ADPKD shows interfamilial and intrafamilial variability. We screened for mutations the 3' region of the PKD1 gene, from exon 43 to exon 46, in a family showing anticipation and Caroli's disease and have found a 28 base pairs deletion in exon 46 (12801del28) and a new DNA variant in exon 43 (12184 C to G conserving Ala 3991) segregating with the disease. The mutation should result in a protein 44 amino acids longer then the wild-type PKD1. This PKD1 mutation manifests as typical adult-onset disease in the father, but in the proband, a 26-year-old man, ADPKD was diagnosed as a newborn and was associated with Caroli's disease at the age of 18 years. A renal biopsy performed in childhood disclosed a predominance of glomerular cysts. Mutation 12801del28 is the first molecular defect associated with Caroli's disease and the PKD1 phenotype. The finding of the same mutation in two different members of the same family with different expression of the disease indicates that the phenotypic variation in ADPKD must be due to modifying factors that may radically affect the course of the disease.

Esophageal variceal bleeding caused by hypoplasia of the portal vein in a patient with the Klippel-Trenaunay syndrome.

The case of a patient affected by Klippel-Trenaunay syndrome presenting with esophageal variceal bleeding caused by hypoplasia of the vena porta is reported. Hemostasis was achieved by performing a proximal spleno-renal shunt. We discuss the likely association of this mesodermal development abnormality and vascular disorders of the portal vein.

Influence of pharmacological agents on portal hemodynamics: basis for its use in the treatment of portal hypertension.

Progress in the knowledge of the pathophysiology of portal hypertension has opened the door to pharmacological treatments, resulting in a dramatic change in the therapeutic approach to portal hypertension. This review summarizes pharmacological agents that have been shown to effectively decrease portal pressure, paying special attention to its mechanisms of action. In addition, the way to monitor response and clinical efficacy of pharmacological agents is reviewed.

Reduction of variceal pressure by propranolol: comparison of the effects on portal pressure and azygos blood flow in patients with cirrhosis.

This study investigated the correlation between changes in hepatic hemodynamics and esophageal variceal pressure--measured with a noninvasive, pressure-sensitive endoscopic gauge--in 37 portal-hypertensive cirrhotic patients receiving propranolol (0.15 mg/kg, intravenously; n = 21) or placebo (n = 16) under strict double-blind conditions. Placebo administration had no effect on hepatic venous pressure gradient, azygos blood flow or variceal pressure. Propranolol caused a significant reduction in hepatic venous pressure gradient (from 19.6 +/- 1 to 17.3 +/- 1 mm Hg, p < 0.001), azygos blood flow (from 0.61 +/- 0.06 to 0.39 +/- 0.03 L/min, p < 0.001) and variceal pressure (from 13.1 +/- 0.9 to 10.2 +/- 0.9 mm Hg, p < 0.001). In eight patients (propranolol nonresponders) hepatic venous pressure gradient was not modified or decreased by less than 10% after propranolol (mean change, -4.1 +/- 1.6%). However, we found no significant differences between propranolol responders and nonresponders with regard to the decrease in variceal pressure (3.3 +/- 0.7 vs. 2.3 +/- 1.4 mm Hg) and azygos blood flow (0.23 +/- 0.07 vs. 0.21 +/- 0.07 L/min). As expected, in most propranolol responders (11 of 13), reduction in hepatic venous pressure gradient was accompanied by a similar response in variceal pressure (> 10% decrease). However, among propranolol nonresponders, in terms of reduction in hepatic venous pressure gradient, four out of eight patients had decreases greater than 10% in variceal pressure. The results of this study confirm that reduction in hepatic venous pressure gradient by propranolol is associated with a significant decrease in variceal pressure and azygos blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiology of primary sclerosing cholangitis in Spain. Spanish Association for the Study of the Liver.

The incidence of primary sclerosing cholangitis has been estimated on the basis of its frequent association with ulcerative colitis, but direct epidemiologic studies have not yet been carried out. In the current study we report a survey of clinical and epidemiological aspects of primary sclerosing cholangitis in Spain. A questionnaire was circulated to physicians in 33 hospitals throughout Spain to ascertain the number and the clinical, biochemical and immunologic characteristics of patients with primary sclerosing cholangitis from January 1, 1984 to December 31, 1988. Twenty-three centers, from 12 Spanish regions, covering a population of 19.23 million answered the questionnaire. Forty-three patients (60.5% males) with a mean age of 42.3 years (range 12 to 75 years) were seen during the 5-year period. At presentation, 16% of the cases were asymptomatic. Ulcerative colitis was present in 44.2% of cases, and one patient had Crohn's disease. The overall annual incidence ranged from 0.16 to 0.68 cases/million from 1985 to 1988, and the annual prevalence increased from 0.78 cases/million in 1984 to 2.24 cases/million in 1988. No geographical differences were found, but there was a trend to detect more cases in industrialized regions. In conclusion, there was a continuing rise in the annual incidence and prevalence of primary sclerosing cholangitis in Spain over a 5-year period.

[Meningeal infiltration in multiple myeloma. Study of a new case and literature review]. / Infiltración meníngea en el mieloma múltiple. Estudio de un nuevo caso y revisión de la bibliografía.

A patient with lambda light-chains Bence-Jones multiple myeloma (MM) showed a meningeal myelomatosis during a relapse of his illness. Meningeal infiltration was showed through the detection of plasmatic cells in cerebro spinal fluid, identified morphologic and immunophenotypically, together with hyperproteinemia constituted exclusively by lambda light-chains. Treatment was given, intrathecal (methotrexate and cytosine arabinoside) and systemic (vincristine, adriamycin and dexamethasone) chemotherapy, with disappearance of meningeal infiltration. However the patient died, after three months evolution of MM, tough. Literature on this topic is reviewed.

Effects of isosorbide-5-mononitrate on variceal pressure and systemic and splanchnic haemodynamics in patients with cirrhosis.

BACKGROUND: Isosorbide-5-mononitrate is a long-acting nitrovasodilator which was introduced for the treatment of portal hypertension because of its capacity to reduce portal pressure. In contrast to vasoconstrictors, isosorbide-5-mononitrate acts primarily by decreasing portal-collateral resistance without deleterious effects on liver function, although at high doses, a reflex splanchnic vasoconstriction elicited by the fall in arterial pressure may further decrease portal pressure. However, there is no information on the effects of isosorbide-5-mononitrate on variceal pressure, which is thought to be a major determinant of variceal haemorrhage. METHODS: We investigated the effects of isosorbide-5-mononitrate (40 mg, orally; n = 12) or placebo (n = 10) on variceal pressure (non-invasive endoscopic gauge) and hepatic haemodynamics in 22 patients with cirrhosis. RESULTS: Placebo administration had no significant effects. In contrast, isosorbide-5-mononitrate significantly reduced variceal pressure (from 13.5 +/- 3.6 to 9.8 +/- 3.2 mmHg, p < 0.005). This was associated with a fall in wedged hepatic venous pressure (from 28 +/- 5.8 to 25.9 +/- 6.2 mmHg, p < 0.005), hepatic venous pressure gradient (from 20 +/- 4 to 18 +/- 4.7 mmHg, p < 0.005) and azygos blood flow (from 668 +/- 197 to 597 +/- 160 ml/min, p < 0.05), suggesting that the decrease in variceal pressure caused by isosorbide-5-mononitrate could be caused by both reductions in collateral resistance and collateral blood flow. Isosorbide-5-mononitrate moderately reduced mean arterial pressure (-13 +/- 16%; p < 0.005), its fall being directly related to the fall in hepatic venous pressure gradient (r = 0.6, p < 0.01). CONCLUSIONS: The results of this study show that isosorbide-5-mononitrate markedly and significantly reduces variceal pressure in patients with cirrhosis and provide further support for its clinical use in the pharmacological treatment of portal hypertension.

Time profile of the haemodynamic effects of terlipressin in portal hypertension.

BACKGROUND/AIMS: Terlipressin is a long-acting vasopressin analogue that has been proved useful in the treatment of variceal haemorrhage. This study investigates the time profile of the haemodynamic effects of terlipressin on portal hypertension as well as the efficacy in decreasing portal-pressure and collateral blood flow of reduced doses, suitable for longer therapy to prevent early rebleeding. METHODS: Splanchnic and systemic haemodynamics were measured in 23 patients with cirrhosis and portal hypertension in baseline conditions and at 30 min, 1, 2, 3 and/or 4 h after the double-blind administration of a single intravenous injection of 1 mg (n=8) or 2 mg (n=8) of terlipressin, or placebo (n=7). RESULTS: Placebo caused no significant effects. At 30 min of terlipressin administration, the hepatic venous pressure gradient (1 mg: -16+/-9%, 2 mg: -21+/-11%; p<0.01) and azygos blood flow (1 mg: -19+/-13%, 2 mg: -25+/-17%; p<0.05) were significantly reduced. These effects were still significant at 4 h (2 mg) or 3 h (1 mg). Both doses moderately increased arterial pressure at 1 h. At 4 h, neither arterial pressure nor peripheral vascular resistance was significantly modified by either dose of terlipressin. Terlipressin caused no significant changes in hepatic blood flow. CONCLUSIONS: In patients with cirrhosis, a single injection of 2 mg of terlipressin significantly and markedly reduces portal pressure and azygos blood flow for up to 4 h. The effects of a reduced dose (1 mg) were almost as pronounced and prolonged, suggesting that after the initial control of variceal bleeding, terlipressin therapy could be maintained for several days at low dosage to reduce the risk of early rebleeding.

Endoscopic assessment of variceal volume and wall tension in cirrhotic patients: effects of pharmacological therapy.

BACKGROUND & AIMS: Variceal rupture is believed to occur when variceal wall tension is excessive. The combined use of endosonography, allowing the objective measurement of variceal radius, and endoscopic measurement of transmural variceal pressure may enable assessment of this important parameter. The aim of this study was to assess the effects on variceal hemodynamics of drugs acting through different mechanisms: decreasing portocollateral blood flow (propranolol) or resistance (isosorbide-5-mononitrate [ISMN]). METHODS: Repeated measurements of variceal radius, volume (by endosonography), and transmural pressure (using endoscopic gauge) were performed in 27 cirrhotic patients at baseline and 40 minutes after double-blind administration of placebo (n = 9), propranolol (n = 9), or ISMN (n = 9). RESULTS: Placebo had no effect. Propranolol significantly reduced variceal volume (-32% +/- 26%; P = 0.01), radius (-12% +/- 9%; P < 0.005), and pressure (-26% +/- 10%; P < 0.0001). The resulting decrease in wall tension (-34% +/- 13%; P < 0.0005) exceeded that in transmural pressure (P < 0.01). ISMN reduced transmural variceal pressure (-26% +/- 21%; P < 0.005), but not radius (-3% +/-14%; NS) and volume (-9% +/- 31%; NS). CONCLUSIONS: The combination of endosonography and endoscopic measurement of transmural variceal pressure allows quantitative estimation of variceal wall tension. Propranolol and ISMN reduce similarly transmural variceal pressure. Propranolol, but not ISMN, reduces variceal volume and radius. Therefore, despite similar decreases in variceal wall tension, propranolol may offer a greater therapeutic effect than ISMN in portal hypertension.

Platelet cytosolic calcium concentration in patients with liver cirrhosis. Relationship with hepatic and systemic hemodynamics.

BACKGROUND/AIMS: Due to structural and functional similarities between platelets and vascular smooth muscle cells, platelet cytosolic calcium concentration ([Ca2+]i) has been suggested to be a useful tool to study regulatory mechanisms of peripheral vascular tone. The aim of the present study was to investigate platelet [Ca2+]i in patients with cirrhosis and whether this parameter is related with the systemic and splanchnic vasodilatation found in these patients. METHODS: Seventeen patients with cirrhosis and eight age- and sex-matched controls were studied. Mean arterial pressure, cardiac output, femoral blood flow and basal and thrombin-stimulated platelet [Ca2+]i were measured. Cardiac output (thermal dilution), azygos blood flow, hepatic venous pressure gradient and hepatic blood flow were also measured in patients with cirrhosis. RESULTS: Patients with cirrhosis had severe portal hypertension and a significantly higher cardiac output and femoral blood flow and a significantly lower systemic and femoral vascular resistance than controls. Patients with cirrhosis had a lower basal platelet [Ca2+]i than normal subjects. However, there was no relationship between platelet [Ca2+]i and any of the hemodynamic parameters that evaluate systemic or splanchnic vasodilatation. CONCLUSIONS: This study shows that cirrhotic patients with portal hypertension have a significant reduction in platelet basal [Ca2+]i. The lack of correlation between platelet [Ca2+]i and hepatic and systemic hemodynamics does not support the use of platelet [Ca2+]i as a model to study mechanisms involved in the pathophysiology of the hyperdynamic circulation associated to portal hypertension.

Predictive value of the variceal pressure response to continued pharmacological therapy in patients with cirrhosis and portal hypertension.

Noninvasive measurements of variceal pressure adequately reflect the hemodynamic effects of propranolol on portal hypertension. However, the prognostic value of variceal pressure responses during continued propranolol therapy has not been evaluated, and it is unclear whether this may substitute invasive measurements of portal pressure response. Fifty-five portal hypertensive patients with cirrhosis were studied before and at 4 months of continued propranolol therapy. Variceal pressure was measured using an endoscopic pressure gauge. Portal pressure was evaluated as the hepatic venous pressure gradient (HVPG). Over a 28 +/- 11 month follow-up, 16 patients experienced variceal bleeding. Baseline characteristics were similar in bleeders and nonbleeders. At 4 months, reduction in variceal pressure was less marked in bleeders than in nonbleeders (5% +/- 20% vs. -15% +/- 24%; P =.03). A fall in variceal pressure 20% or greater of baseline was an independent predictor of absence of variceal bleeding; which occurred in 5% of patients with a 20% or greater fall in variceal pressure versus 42% of patients with less than a 20% reduction (P =.004). The HVPG response had similar independent prognostic value (decrease > or =20%: 6% bleeding; decrease <20%: 45% bleeding; P =.004) but identified different patients. Achieving a 20% decrease in either variceal pressure or HVPG was highly sensitive (85%) and specific (93%) identifying patients not bleeding on follow-up. Endoscopic measurements of variceal pressure response to continued pharmacotherapy provide useful prognostic information on the risk of variceal bleeding. As with HVPG response, a fall in variceal pressure of 20% or greater is associated with a very low risk of variceal bleeding. The combination of both parameters allows almost optimal prognostication.