Epidemiology of bacterial infections in patients with liver cirrhosis. Experience in a Spanish tertiary health center.

INTRODUCTION: Bacterial infections represent a serious complication of liver cirrhosis. Traditionally, Gram negative bacteria have been described as the microorganisms responsible for the majority of the infections. However, in the past few years, changes in the microbiological spectrum have been described, and multiresistant bacteria are observed more frequently.  OBJECTIVE: To assess the proportion of patients with infections caused by multiresistant bacteria admitted to our hospital, and to obtain information about their epidemiology, risk factors and clinical impact.  MATERIALS AND METHODS: We performed a retrospective evaluation of 294 cirrhotic patients admitted to our unit due to infection between June, 2011, and June, 2013.  RESULTS: We isolated 310 microorganisms from 294 patients; 109 (35.2%) were Gram positive, 167 (53.9%), Gram negative, and 34, fungi (11%). As for the microbiological agents, the most frequent was Escherichia coli (98 isolations). The infection was community-acquired in 22.9% of cases, healthcareassociated in 38.1% and nosocomial in 39%. Worse liver infections and septic shock were more frequent among patients with multiresistant isolates (p=0.05); and intrahospital mortality was also higher among them (p=0.017). Previous hospital admission, antibiotic treatment 60 days before, nosocomial or healthcare-associated acquisition and bacterial isolation in control cultures were identified as possible risk factors for the development of multiresistant infection.  DISCUSSION: The results of our study confirm that important changes have ocurred in the microbiological spectrum of bacterial infections in patients with liver cirrhosis. Multiresistant bacteria are associated with high morbidity and mortality, as well as failure of traditional antibiotic treatment. Successfull control of the infection requires an early identification of patients at risk.

Liver Support With Albumin Dialysis Reduces Hepatitis C Virus Viremia and Facilitates Antiviral Treatment of Severe Hepatitis C Virus Recurrence After Liver Transplantation.

Patients with severe hepatitis C virus (HCV) recurrence after liver transplantation (LT) present an ominous prognosis, rarely achieving sustained virological response (SVR). Dialysis procedures may transiently decrease the HCV viral load, but the effect of albumin dialysis is currently unknown. Here, we evaluated the impact of albumin dialysis using the Molecular Adsorbent Recirculating System (MARS) used as a co-adjuvant antiviral treatment for severe HCV recurrence after LT. Thirteen patients (11 males, median age 48 years) with fibrosing cholestatic hepatitis or METAVIR fibrosis score ≥ F3 with severe portal hypertension underwent three consecutive MARS sessions. Antiviral therapy was initiated in 11 patients within 24 h after the MARS sessions. A contemporary cohort of seven patients who did not follow the MARS protocol is shown for comparison. MARS treatment resulted in consistent decreases of viral load from 7.59 log10 IU/mL [6.15-8.90] to 6.79 log10 IU/mL [5.18-7.84] (P = 0.003) as well as in decreases of serum bilirubin, gamma-glutamyl transpeptidase, alanine aminotransferase and aspartate aminotransferase (all P < 0.05). The overall rate of SVR was 0% in the Control group and 54.6% in patients initiating antiviral therapy within 24 h after MARS. Survival at 1 and 3 years was, respectively, 93% and 70% in patients undergoing MARS, compared with 29% and 14% in the Control group (P = 0.001). No major adverse events related to MARS treatment were observed. In conclusion, the use of MARS may facilitate the achievement of SVR and improve the prognosis of patients with severe HCV-recurrence after LT by reducing viral load and improving liver function prior to antiviral therapy.

Epidemiología de las infecciones bacterianas en pacientes con cirrosis hepática, experiencia de un centro español de atención terciaria / Epidemiology of bacterial infections in patients with liver cirrhosis. Experience in a Spanish tertiary health center

Introducción. Las infecciones bacterianas representan una complicación grave de la cirrosis. En los últimos años se han observado cambios en el espectro microbiológico de estas infecciones, fundamentalmente, el aumento de infecciones por gérmenes multirresistentes. Objetivo. Establecer la proporción de infecciones por microorganismos multirresistentes en pacientes cirróticos ingresados en un centro de atención de Madrid, y analizar su epidemiología, factores de riesgo e impacto clínico. Materiales y métodos. Se hizo un estudio retrospectivo en el cual se evaluaron 294 pacientes hospitalizados por infección bacteriana en el Hospital General Universitario Gregorio Marañón de Madrid, entre junio de 2011 y junio de 2013. Resultados. Se aislaron 310 microorganismos de 223 pacientes; 109 (35,2 %) eran Gram positivos, 167 (53,9 %), Gram negativos, y 34 (11 %), hongos. El agente etiológico más frecuente fue Escherichia coli (98 aislamientos). Las infecciones se habían adquirido en la comunidad en 22,9 % de los casos, se asociaron con la atención de salud en 38,1 % y se adquirieron durante la estancia hospitalaria en 39 %. Los pacientes con aislamientos multirresistentes desarrollaron con más frecuencia choque séptico (p=0,05), y presentaron peor función hepática y alta mortalidad durante la estancia hospitalaria (p=0,017). El ingreso previo, el uso de antibióticos en los 60 días anteriores, la adquisición de la infección en el hospital o asociada a un ingreso reciente y el aislamiento de bacterias en los cultivos de control, se determinaron como posibles factores de riesgo para el desarrollo de la infección multirresistente. Discusión. Los resultados del estudio confirmaron que el espectro microbiológico de las infecciones bacterianas en pacientes con cirrosis ha sufrido importantes cambios. Las infecciones por gérmenes multirresistentes causan infecciones con gran morbimortalidad y el fracaso del tratamiento antibiótico habitual. Para controlarlas de forma eficaz, es imprescindible detectar precozmente a aquellos pacientes con factores de riesgo.

Introduction: Bacterial infections represent a serious complication of liver cirrhosis. Traditionally, Gram negative bacteria have been described as the microorganisms responsible for the majority of the infections. However, in the past few years, changes in the microbiological spectrum have been described, and multiresistant bacteria are observed more frequently. Objective: To assess the proportion of patients with infections caused by multiresistant bacteria admitted to our hospital, and to obtain information about their epidemiology, risk factors and clinical impact. Materials and methods: We performed a retrospective evaluation of 294 cirrhotic patients admitted to our unit due to infection between June, 2011, and June, 2013. Results: We isolated 310 microorganisms from 294 patients; 109 (35.2%) were Gram positive, 167 (53.9%), Gram negative, and 34, fungi (11%). As for the microbiological agents, the most frequent was Escherichia coli (98 isolations). The infection was community-acquired in 22.9% of cases, healthcare-associated in 38.1% and nosocomial in 39%. Worse liver infections and septic shock were more frequent among patients with multiresistant isolates (p=0.05); and intrahospital mortality was also higher among them (p=0.017). Previous hospital admission, antibiotic treatment 60 days before, nosocomial or healthcare-associated acquisition and bacterial isolation in control cultures were identified as possible risk factors for the development of multiresistant infection. Discussion: The results of our study confirm that important changes have ocurred in the microbiological spectrum of bacterial infections in patients with liver cirrhosis. Multiresistant bacteria are associated with high morbidity and mortality, as well as failure of traditional antibiotic treatment. Successfull control of the infection requires an early identification of patients at risk.

Use of artificial intelligence as an innovative donor-recipient matching model for liver transplantation: results from a multicenter Spanish study.

BACKGROUND & AIMS: There is an increasing discrepancy between the number of potential liver graft recipients and the number of organs available. Organ allocation should follow the concept of benefit of survival, avoiding human-innate subjectivity. The aim of this study is to use artificial-neural-networks (ANNs) for donor-recipient (D-R) matching in liver transplantation (LT) and to compare its accuracy with validated scores (MELD, D-MELD, DRI, P-SOFT, SOFT, and BAR) of graft survival. METHODS: 64 donor and recipient variables from a set of 1003 LTs from a multicenter study including 11 Spanish centres were included. For each D-R pair, common statistics (simple and multiple regression models) and ANN formulae for two non-complementary probability-models of 3-month graft-survival and -loss were calculated: a positive-survival (NN-CCR) and a negative-loss (NN-MS) model. The NN models were obtained by using the Neural Net Evolutionary Programming (NNEP) algorithm. Additionally, receiver-operating-curves (ROC) were performed to validate ANNs against other scores. RESULTS: Optimal results for NN-CCR and NN-MS models were obtained, with the best performance in predicting the probability of graft-survival (90.79%) and -loss (71.42%) for each D-R pair, significantly improving results from multiple regressions. ROC curves for 3-months graft-survival and -loss predictions were significantly more accurate for ANN than for other scores in both NN-CCR (AUROC-ANN=0.80 vs. -MELD=0.50; -D-MELD=0.54; -P-SOFT=0.54; -SOFT=0.55; -BAR=0.67 and -DRI=0.42) and NN-MS (AUROC-ANN=0.82 vs. -MELD=0.41; -D-MELD=0.47; -P-SOFT=0.43; -SOFT=0.57, -BAR=0.61 and -DRI=0.48). CONCLUSIONS: ANNs may be considered a powerful decision-making technology for this dataset, optimizing the principles of justice, efficiency and equity. This may be a useful tool for predicting the 3-month outcome and a potential research area for future D-R matching models.

Oral probiotic VSL#3 attenuates the circulatory disturbances of patients with cirrhosis and ascites.

BACKGROUND & AIMS: The modulation of gut flora constitutes a therapeutic tool in patients with liver disease, but some of its modalities require further investigation. Here, we evaluated the effects of probiotics on the hepatic and systemic haemodynamic alterations of advanced liver disease. METHODS: Seventeen patients with cirrhosis and ascites were prospectively included, five of whom abandoned this study prematurely. Hepatic and systemic haemodynamic evaluations were performed at baseline and after 6 weeks of receiving an oral VSL#3 probiotic preparation. Peripheral blood analyses included the evaluation of cytokines (TNF-alpha, IL-1beta, IL-6), bacterial translocation [bacterial DNA and lipopolysaccharide-binding protein (LBP)] and nitric oxide end-products (NOx). RESULTS: In 12 patients completing this study, the oral administration of VSL#3 resulted in reductions of the hepatic venous pressure gradient (HVPG, P < 0.001), cardiac index and heart rate (both P < 0.01) and in increases of the systemic vascular resistance (P < 0.05) and mean arterial pressure (P = 0.06). HVPG decreased at least 10% from baseline in eight patients (67%). Serum sodium increased in most patients (P < 0.01). All these changes were unrelated to the detection of bacterial DNA or to the levels of LBP, pro-inflammatory cytokines or NOx. No significant adverse effects were observed. CONCLUSION: Administration of the probiotic mixture VSL#3 improved the hepatic and systemic haemodynamics and serum sodium levels in patients with cirrhosis. Our results identify major effects of probiotics in liver disease and provide the rationale for assessing their therapeutic potential against the progression of portal hypertension and its complications in future clinical trials.

Serum level of soluble vascular cell adhesion molecule in patients with hepatocellular carcinoma and its association with severity of liver disease.

BACKGROUND: VCAM-1 (soluble vascular cell adhesion molecule-1) plays a role in liver angiogenesis. Hepatocellular carcinoma (HCC) has important angiogenic activity, so expression of VCAM-1 may be pathogenic. AIM: To assess the association between serum VCAM-1 (sVCAM-1) levels and features of tumour and liver disease in patients with and without HCC, and to study the influence of HCC treatment on sVCAM-1 levels. MATERIAL AND METHODS: Concentrations in peripheral (sVCAM-1-P) and hepatic (sVCAM-1-H) veins were analysed using ELISA in 134 consecutive patients with chronic liver disease between May 2004 and February 2006, who underwent a splanchnic haemodynamic study. Of these patients, 58 had HCC. RESULTS: sVCAM-1-P and sVCAM-1-H were well correlated in both groups. No association was found between sVCAM-1-H and tumour features. No differences were observed in sVCAM-1-H between HCC and non-HCC cirrhotic patients. There was a significant linear association between Child-Pugh stage and sVCAM-1-H in HCC-patients (Child-Pugh A [2,485 ± 1,294 ng/mL] vs. Child-Pugh B [3,408 ± 1,338 ng/mL] vs. Child-Pugh C [4,096 ± 862 ng/mL]; p = 0.007). Seven non-cirrhotic HCC patients had a significantly lower sVCAM-1-H than cirrhotic HCC patients. Treatment of HCC leads to an increase in sVCAM-1-H levels although this was not associated with the necrosis response to treatment. CONCLUSIONS: sVCAM-1 levels are more closely associated with the severity of underlying liver disease than with the presence of HCC. sVCAM-1 levels are not associated with tumour features or invasiveness; therefore, sVCAM-1 does not seem to play an important role in the angiogenic processes of HCC.

Prognostic value of hepatic venous pressure gradient in patients with compensated chronic hepatitis C-related cirrhosis.

BACKGROUND AND AIM: Hepatic venous pressure gradient (HVPG) is the main predictor of clinical decompensation in cirrhotic patients with compensated disease of any etiology without varices. However, the predictive factors of decompensation are not so well known in patients with hepatitis C-related compensated cirrhosis, in whom etiology-based therapy is difficult. The aim of this study was to identify predictors of decompensation in patients with compensated chronic hepatitis C (CHC)-related cirrhosis with and without esophageal varices (Baveno stages 1 and 2). METHODS: The study population was a cohort of 145 of such consecutive patients who received hepatic hemodynamic study. All patients were similarly followed every 6 months. Through multivariate Cox regression and bootstrap analyses, a prognostic index (PI) was developed and tested in an external cohort (n = 38). RESULTS: Forty-two patients (29%) suffered a first decompensation episode after a median follow-up of 27 months (2-110). Cox regression analysis identified HVPG (hazard ratio (HR) 1.11; 95% confidence interval (CI): 1.05-1.17) and albumin (HR 0.42; 95% CI: 0.22-0.82) as independent predictors of decompensation. Bootstrapping confirmed that HVPG (95% CI: 1.05-1.18) and albumin (95% CI: 0.12-0.74) were the most robust predictive variables. Using a cut-off level of 2.5, the PI [4 + (0.11 × HVPG - 0.8 × albumin)] was able to distinguish two populations of patients with very different risks of decompensation in both the exploratory and validation cohorts. A time-dependent ROC curve identified HVPG as the best predictive variable. CONCLUSION: HVPG and albumin are independent predictors of clinical decompensation in patients with compensated CHC-related cirrhosis irrespective of the existence of varices.

Serum angiopoietin-2 level as a predictor of tumor invasiveness in patients with hepatocellular carcinoma.

BACKGROUND: Because hepatocellular carcinoma (HCC) has important angiogenic activity, the expression of angiopoietin-2 (Ang-2) may have a pathogenic role. The information about the influence of serum Ang-2 (sAng-2) in patients with HCC is scarce. AIMS: The aim was to assess the association between sAng-2 levels and characteristics of tumor and liver disease in patients with HCC. METHODS: sAng-2 concentrations in peripheral (sAng-2-P) and hepatic (sAng-2-H) veins were analyzed by ELISA in 33 patients with chronic liver disease who underwent a splanchnic hemodynamic study. Thirty-two patients received treatment for HCC. RESULTS: The median age was 61 years and 79% were male. Hepatitis C infection (70%) was the main etiology. Most patients were Child-Pugh grade A (72.7%). sAng-2-P and sAng-2-H were well correlated (r = 0.95; p < 0.0001). A significant association was found between sAng-2-H and lobar tumor extension, vascular thrombosis, BCLC staging, infiltrating pattern, abnormal alpha-fetoprotein level, fulfillment of the Milan criteria, and performance of nonsystemic treatment. sAng-2-H also showed a significant correlation with the MELD score (r = 0.49; p = 0.007), albumin (r = -0.63; p < 0.001), and HVPG (r = 0.44; p = 0.02). Eleven patients received treatment with radiofrequency ablation and eight with transarterial chemoembolization. HCC treatment did not influence the sAng-2 concentration while the necrosis response to treatment was not influenced by previous sAng-2 levels. CONCLUSIONS: Ang-2 seems to play an important role in the angiogenic processes of HCC and its serum levels are associated with tumor characteristics and invasive behavior. Our results suggest that Ang-2 is not related with treatment response and its level is not modified by treatment.

[Influence of treatment of hepatocellular carcinoma before liver transplantation on post transplant tumor recurrence and survival]. / Influencia del tratamiento del hepatocarcinoma antes del trasplante hepático en la recurrencia tumoral y supervivencia postrasplante.

OBJECTIVES: To evaluate the effectiveness of treatment of hepatocellular carcinoma (HCC) before liver transplantation (LT) and its influence on survival and tumor recurrence in patients transplanted for HCC. PATIENTS AND METHODS: We included 67 liver transplant patients with a preoperative diagnosis of HCC and pathological confirmation in the native liver between January 2000 and October 2007. Treatment before LT was performed in 46 (68.7%) patients [radiofrequency ablation in 18, transarterial chemoembolization in 31 and percutaneous ethanol injection in two]. RESULTS: The median time between inclusion on the waiting list and LT was 4 months and was similar in treated and untreated patients. The median time between pre-transplantation locoregional therapy and LT was less than 6 months in 65.2% of the patients. Treated patients had better liver function (Child A 52.2 vs 19%; Child B 39.1 vs 33.3%; Child C 8.7 vs. 47.6%; p=0.001) and a higher proportion of total tumor size > 3 cm (59.1% vs 30%; p=0.031). Total tumor necrosis was observed in 26.1% of the patients, with no differences according to treatment modality or tumor size. Tumor recurrence occurred in six patients (9%). The median time between LT and tumor recurrence was 26.5 months with a subsequent median survival of 6.6 months. Overall survival was 83.5%, 69.9% and 59.5%, and tumor recurrence-free survival was 83.5%, 68.3% and 58% at 1, 3 and 5 years, respectively. Previous HCC treatment showed no influence on survival or tumor recurrence. Likewise, the grade of tumor necrosis was unrelated to overall survival or the probability of recurrence. CONCLUSION: Treatment of HCC before LT in patients with a waiting list time of less than 6 months does not appear to influence survival or tumor recurrence.

Portal hypertensive colopathy is associated with portal hypertension severity in cirrhotic patients.

AIM: To assess the prevalence of portal hypertension (PH) related colorectal lesions in liver transplant candidates, and to evaluate its association with the severity of PH. METHODS: Between October 2004 and December 2005, colonoscopy was performed in 92 cirrhotic liver transplant candidates. We described the lesions resulting from colorectal PH and their association with the grade of PH in 77 patients who underwent measurement of hepatic venous pressure gradient (HVPG). RESULTS: Mean age was 55 years and 80.7% of patients were men. The main etiology of cirrhosis was alcoholism (45.5%). Portal hypertensive colopathy (PHC) was found in 23.9%, colonic varices in 7.6% and polyps in 38% of patients (adenomatous type 65.2%). One asymptomatic patient had a well-differentiated adenocarcinoma. The manifestations of colorectal PH were not associated with the etiology of liver disease or with the Child-Pugh grade. Ninety percent of patients with colopathy presented with gastroesophageal varices (GEV), and 27.5% of patients with GEV presented with colopathy (P = 0.12). A relationship between higher values of HVPG and presence of colopathy was observed (19.9 +/- 6.2 mmHg vs 16.8 +/- 5.4 mmHg, P = 0.045), but not with the grade of colopathy (P = 0.13). Preneoplastic polyps and neoplasm (P = 0.02) and spontaneous bacterial peritonitis (P = 0.006) were more prevalent in patients with colopathy. We did not observe any association between previous beta-blocker therapy and the presence of colorectal portal hypertensive vasculopathy. CONCLUSION: PHC is common in cirrhotic liver transplant candidates and is associated with higher portal pressure.

[Results of colonoscopic examination in the evaluation of cirrhotic candidates for liver transplantation]. / Resultados de la realización de colonoscopia en la evaluación de pacientes cirróticos candidatos a trasplante hepático.

AIM: To assess the presence of preneoplastic and neoplastic colonic lesions, as well as those related to portal hypertensive vasculopathy, and their association with liver disease in cirrhotic patients who are candidates for orthotopic liver transplantation (LT). METHODS: Between October 2004 and December 2005, colonoscopy was performed in 92 patients who were LT candidates, aged >50 years old or aged <50 years old but with clinical indications. RESULTS: Eighty-eight percent of the patients were > 50 years old, the mean age was 55.3 years (29-69) and 81.5% were males. The main etiology of cirrhosis was alcoholic (46.7%), and 21% were Child-Pugh class A. No abnormalities were detected in 20.7%. Polyps were discovered in 38% (35/92) of patients (adenomatous 65.2%; tubular type 86.7%). Six patients with adenomatous polyps had mild dysplasia, and one asymptomatic patient had a well-differentiated adenocarcinoma. An association was found between polyps and male sex (44% males vs 17.6% females; p=0.044) and Child-Pugh grade (63.2% Child A vs 32.9% Child B/C, p=0.016) but not with serum levels of carcinoembryonic antigen (CEA), age or etiology of liver disease. Portal hypertensive colopathy was found in 23.9%, rectal varices in 7.6% and internal or mixed hemorrhoids in 52.3%. CONCLUSION: The prevalence of preneoplastic and neoplastic colonic lesions may support the use of colonoscopy in LT candidates aged >50 years-old or with a history suggesting lower gastrointestinal bleeding or other abnormalities.

Risk factors for developing de novo autoimmune hepatitis associated with anti-glutathione S-transferase T1 antibodies after liver transplantation.

De novo autoimmune hepatitis (de novo AIH) is a rare form of graft dysfunction that develops after liver transplantation (LT) in patients transplanted for conditions other than autoimmune disorders. Although characterized by biochemical, serological, and histological features of AIH, de novo AIH is sometimes associated with atypical serum autoantibodies, many of which are directed against glutathione S-transferase T1 (anti-GSTT1). GSTT1 donor/recipient genotype mismatch has been suggested as a necessary condition for the appearance of autoantibodies and de novo AIH. However, clinically evident disease is not observed in all patients with anti-GSTT1 antibodies. We examined the incidence of de novo AIH and its conditioning (risk) factors in patients with anti-GSTT1 antibodies. Anti-GSTT1 autoantibodies were detected in 29 of 419 [6.9%; 95% confidence interval (CI), 4.9-9.8] consecutive adult LT recipients with donor/recipient GSTT1 mismatch. Twenty of 27 assessable patients (74%) developed de novo AIH after a median follow-up of 26 months (95% CI, 19.2-32.8). The probability of de novo AIH was 11%, 44%, and 60% 12, 24, and 36 months after LT, respectively. No relationship emerged between de novo AIH and recipient gender, donor and recipient age, rejection episodes, immunosuppressive regime, allelic GSTT1 expression, human leukocyte antigen distribution, or cytomegalovirus infection. Multivariate analysis identified male donor [hazard ratio (HR), 3.3; 95% CI, 1.18-9.26; P = 0.018], nonalcoholic etiology (HR, 4.67; 95% CI, 1.64-13.3; P = 0.002), and high anti-GSTT1 titer (HR, 2.98; 95% CI, 1.04-8.57; P = 0.035) as independent predictors of de novo AIH. Most patients with anti-GSTT1 antibodies and donor/recipient GSTT1 mismatch developed clinically evident de novo AIH after LT. The risk of developing the disease was increased by male donor gender, nonalcoholic etiology of original liver disease, and a high anti-GSTT1 titer.

Pamidronate in the prevention of bone loss after liver transplantation: a randomized controlled trial.

Rapid bone loss and high rates of fractures occur following liver transplantation. To analyze the effect of intravenous pamidronate on bone loss after liver transplantation. A randomized, double-blind, placebo-controlled study was performed. Seventy-nine patients were randomized to two groups of treatment: the pamidronate group (n = 38) was treated with 90 mg/IV of pamidronate within the first 2 weeks and at 3 months after transplantation; the placebo group (n = 41) received glucose infusions at the same time points. All patients received calcium and vitamin D. Bone mineral density (BMD) at the lumbar spine (L(2)-L(4)) and proximal femur using dual energy X-ray absorptiometry and also spinal X-rays were performed before, and at 6 and 12 months after liver transplantation. Biochemical and hormonal determinations were performed previous to transplantation, at 24 h before and after treatment, as well as at 6 and 12 months after liver transplantation. At 12 months after transplantation, there were significant differences in lumbar BMD changes (6 months: pamidronate 1.6% vs. placebo 0.8%, P = NS; 12 months: pamidronate 2.9% vs. placebo 1%, P < 0.05). Femoral neck BMD decreased in the pamidronate- and placebo groups during the first 6 months (6 months: pamidronate -3.1% vs. placebo -2.9%, P = NS; 12 months: pamidronate -3.2% vs. placebo -3.1%, P = NS). BMD at the trochanter remained stable in the pamidronate group, whilst a reduction was observed in the placebo group at 6 months (6 months: pamidronate -0.7% vs. placebo -3.7%, P < 0.05; 12 months: pamidronate -0.5% vs. placebo -1.2%, P = NS). Moreover, no significant differences in the incidence of fractures, serum parathyroid hormone and serum 25-hydroxyvitamin D values between both groups were found. Pamidronate did not increase the risk of serious adverse events. The results of this study show that 90 mg of intravenous pamidronate within the first 2 weeks and at 3 months following liver transplantation preserve lumbar bone mass during the first year, without significant adverse events. However, pamidronate does not reduce bone loss at the femoral neck and furthermore it does not reduce skeletal fractures.

[Accreditation of processes in hepatology]. / Acreditación de procesos en hepatología.

The Spanish Association for the Study of the Liver decided in 2006 to develop a project to assess the quality of the professionals, processes and medical units dealing with the management of patients with liver diseases in Spain. The current article reports the criteria proposed to assess the quality and the accreditation of the processes in hepatology. The processes considered include most patients with liver diseases and the accreditation system designed is highly specific. This document, together with a previous one published in gastroenterología y hepatología concerning the accreditation of the professionals and a third document dealing with the accreditation of liver units that will be published soon, form the basis of the quality assessment of hepatology in our country.

Serum levels of soluble vascular cell adhesion molecule are related to hyperdynamic circulation in patients with liver cirrhosis.

BACKGROUND: In patients with liver cirrhosis, serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) have been associated with increasing fibrosis and are related to angiogenesis. AIM: To assess the possible correlation between sVCAM-1 and splanchnic and systemic haemodynamic and clinical staging of cirrhotic patients. METHODS: We assessed, using immunoassays, the serum levels of sVCAM-1, in the peripheral and hepatic vein, in all consecutive patients with liver cirrhosis, who underwent a haemodynamic study as part of its routine clinical work-up. RESULTS: We studied 86 patients [61 M/25 F; age 51.1 (8.3) years] with alcoholic (31) or viral (HBV:6, HCV:49) cirrhosis, 10 of them with hepatocellular carcinoma (Milan criteria). The mean follow-up was 391(187) days; 29 patients died or underwent transplantion during follow-up. A strong correlation in serum levels of sVCAM-1 was observed between the peripheral and the hepatic vein (r=0.8; P=0.0001). There was no correlation between levels of sVCAM-1 and hepatic venous pressure gradient. At univariate analysis, sVCAM-1 was inversely related with mean arterial pressure (r=-0.292; P=0.007), systemic vascular resistance (SVR) (r=-0.37; P=0.005) and serum sodium levels (r=-0.326; P=0.002). In multivariate linear regression only SVR remained as an independent variable associated to sVCAM-1. A correlation of sVCAM-1 with Child-Pugh scores, model for end-stage liver disease (MELD) and the clinical stage proposed in the Baveno IV consensus conference was also observed. Finally, patients who died or underwent transplantion during follow-up had significantly greater values of sVCAM-1 at baseline than those who did not [3505(1329) vs. 2488(1208) P=0.001]. CONCLUSION: This study supports a potential role of sVCAM-1 as a marker of hyperdynamic circulation, closely related to the different stage of liver cirrhosis.

Use of everolimus as a rescue immunosuppressive therapy in liver transplant patients with neoplasms.

Everolimus is a new immunosuppressant with antitumoral properties and few side effects, but limited use in liver transplantation. The aim of the present study was to evaluate the effect on survival and safety of everolimus in post liver transplantation neoplasms in a single center. Ten liver transplant recipients with a posttransplant diagnosis of neoplasm received everolimus during a median of 12.7 (5.5-27.5) months; median survival was 21.3 (7.5-40.5) months. The probability of survival of everolimus group was significantly greater than the observed in a historical cohort of 14 liver recipients with comparable tumors who did not receive everolimus (100%, 90%, 72% vs. 50%, 29%, 14%) at 6, 12, and 24 months, respectively (HR=4.6, 95% confidence interval: 1.3-16.4; P=0.008). During everolimus therapy no patients showed rejection. Renal function improved in three patients. Furthermore, severe adverse effects and infections were infrequent. In summary, everolimus seems safe for liver transplant recipients with cancer and may improve short-term survival, but further studies are needed to determine long-term benefits and safety.

[Importance of hepatology in the current Spanish health environment]. / Importancia de la hepatología en el entorno sanitario, español, actual.

OBJECTIVES: To find out the impact of hepatic diseases on care activity at national and autonomous region level, and in a tertiary hospital with a Hepatology Department. MATERIAL AND METHODS: An analysis was carried out on BMDS data (Basic Minimum Data Set) from 1999 to 2003. In the study of cases from the Gregorio Marañón Hospital, Madrid, data bases from the years 2000-2004 were used, and indicators were calculated, such as the percentages of digestive diseases of the total hospital discharges, of digestive diseases that were admitted into the Digestive Diseases Department, and of the total discharges form this Department that originated from hepatic diseases. RESULTS: Hepatic diseases represented around 23% of the hospital discharges generated by gastroenterology at national level and about the same at autonomous regional level. Hepatocellular carcinoma shows a slow and sustained increase, reaching 22.7% of discharges, due to hepatic disease, in 2003. The mortality specifically due to hepatic disease was around 12% in the year 2003. In the study carried out in a tertiary hospital, 21.2% of the total hospital discharges were due to digestive diseases, in the last year analysed. Only 12.48% of these had been admitted to the Digestive Diseases Department and more than 50% were attributed to Hepatology. CONCLUSIONS: Hepatology is a very important area of health care within Gastroenterology, showing a sustained growth in the last few years.

Antibodies against glutathione S-transferase T1 (GSTT1) in patients with GSTT1 null genotype as prognostic marker: long-term follow-up after liver transplantation.

An objective to improve the evolution of transplants is to identify risk biomarkers of morbidity and loss of allograft. In liver transplant (LTX) recipients, an association has been demonstrated between the presence of mismatch for glutathione S-transferase T1 (GSTT1) and the development of de novo immune hepatitis (IH). In 419 LTX patients we analyzed, for a period of 1 to 14 years, the development of "atypical" autoantibodies directed against GSTT1 and their relationship with the mismatch for GSTT1 genotype and with the risk for developing de novo IH. A total of 6.9% LTX recipients had "atypical" autoantibodies and 24 showed mismatch (recipient/donor) for GSTT1 genotype. From this last group, up to 70% developed de novo IH and graft dysfunction after LTX (95% confidence interval: 17.4-37.5 months). In LTX recipients with a GSTT1 null genotype, the evaluation of "atypical" autoantibodies is useful for monitoring the development of de novo IH.

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.

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.