Disseminated adiaspiromycosis: case report of a liver transplant patient with human immunodeficiency infection, and literature review.

Disseminated adiaspiromycosis is a rare infection that is sometimes associated with immunocompromised situations. We report the case of a patient, infected with human immunodeficiency virus and receiving highly active antiretroviral therapy, who had a liver transplant for hepatocellular carcinoma. The patient presented skin and pulmonary lesions due to adiaspiromycosis during immunosuppressive therapy. A review of >60 cases in the literature shows that adiaspiromycosis is a rare infection and Emmonsia is a dimorphic fungus that is difficult to grow. It should be considered a possible diagnosis in case of fungal infection and pulmonary granulomatosis. We should be aware of emerging adiaspiromycosis in patients with risk factors of immunosuppression, particularly transplant recipients. In these patients in particular, liposomal amphotericin B therapy should be considered.

Usefulness of reagent strips for checking cure in spontaneous bacterial peritonitis after short-course treatment.

BACKGROUND: The usefulness of reagent strips to check cure of spontaneous bacterial peritonitis have not been evaluated to date. AIM: To assess the usefulness of ascitic fluid analysis by means of reagent strips to check cure after a 5-day antibiotic course. METHODS: We prospectively included all cirrhotic patients diagnosed with spontaneous bacterial peritonitis. On day 5, conventional and reagent strip ascitic fluid analyses were performed. RESULTS: Fifty-three episodes of spontaneous bacterial peritonitis in 51 cirrhotic patients were included. Five patients died before the fifth day and in two patients, the control paracentesis yielded no ascitic fluid. In nine out of 46 cases (19.6%), spontaneous bacterial peritonitis had not resolved by day 5. In 32 out of 33 cases in which the ascitic fluid polymorphonuclear count was <250/microL at day five, the reagent strips was negative. The negative predictive value of the reagent strip at fifth day was 97% and the LR- 0.13. CONCLUSIONS: Almost 20% of episodes of spontaneous bacterial peritonitis do not resolve with a short-course of antibiotic treatment. In view of the high negative predictive value and low likelihood ratio for a negative test, reagent strips analysis may be an alternative to conventional cytology if a 5-day antibiotic therapy is planned.

Risk of acute liver injury associated with the use of drugs: a multicentre population survey.

BACKGROUND: Acute liver injury of uncertain aetiology is often drug related and quantitative information about the associated risk is scarce. AIM: To estimate the risk of acute liver injury associated with the use of drugs. METHODS: In a population survey study, 126 cases of acute liver injury were prospectively assembled from January 1993 to December 1999, in patients over 15 years of age, in 12 hospitals in Barcelona (Spain). We estimated the relative risk for each drug as the ratio between the incidence of acute liver injury among the exposed population to the drug and the incidence of acute liver injury among those not exposed to it. Drug consumption data were used to estimate the exposed population. RESULTS: Isoniazid, pyrazinamide, rifampicin, amoxicillin with clavulanic acid, erythromicin, chlorpromazine, nimesulide, and ticlopidine presented the highest risk (point relative risk > 25). Amoxicillin, metoclopramide, captopril and enalapril, furosemide, hydrochlorothiazide, fluoxetine, paroxetine, diazepam, alprazolam, lorazepam, metamizole, low-dose acetylsalicylic acid and salbutamol showed the lowest risk (point relative risk < 5). CONCLUSIONS: This study provides a risk estimation of serious liver disease for various drugs that will be useful in its diagnosis and management, and when comparing with the drug therapeutic benefit in each indication. Some observed associations would be worth specific studies.

Clinical features and outcome of spontaneous bacterial peritonitis in HIV-infected cirrhotic patients: a case-control study.

The aim of this study was to evaluate the clinical characteristics and outcome of spontaneous bacterial peritonitis, a serious complication in patients with cirrhosis and ascites, in an HIV-infected cirrhotic population. Thirty-five HIV-infected cirrhotic patients who developed spontaneous bacterial peritonitis during a 12-year period were compared with 70 non-HIV-infected cirrhotic subjects. Patients were matched according to the date of the first episode of spontaneous bacterial peritonitis. A bacteriological diagnosis was made in 37 of 47 (79%) and in 50 of 97 (52%) episodes in the HIV group and in the non-HIV group, respectively (p=0.003), and Streptococcus pneumoniae was isolated more frequently in the HIV group (22 vs. 8%, p=0.02). Median survival after the initial diagnosis of spontaneous bacterial peritonitis was 2.9 and 14.0 months in the HIV group and non-HIV group, respectively. Age (hazard ratio [HR] 1.04; 95%CI 1.01-1.07), male sex (HR 2.55; 95%CI 1.34-4.83), Child-Pugh score at first spontaneous bacterial peritonitis episode (HR 1.29; 95%CI 1.10-1.54), renal impairment at first spontaneous bacterial peritonitis episode (HR 2.61; 95%CI 1.49-4.62), and HIV infection (HR 9.81; 95%CI 4.03-23.84) were independently associated with higher long-term mortality after the first diagnosis of spontaneous bacterial peritonitis. In conclusion, HIV-infected cirrhotic patients with spontaneous bacterial peritonitis have a higher rate of bacteriological diagnosis and a more frequent pneumococcal etiology than non-HIV-infected subjects. Life expectancy in these patients, once spontaneous bacterial peritonitis has developed, is poor. These data are particularly relevant for determining the optimal time for liver transplantation in this population.

[Domino or sequential liver transplantation. Is it a feasible technique?]. / El trasplante hepático dominó o secuencial, es una técnica factible?

BACKGROUND: In domino liver transplantation (LT), the explanted liver of a patient with familial amyloidotic polyneuropathy (FAP) is donated to another patient. PATIENTS AND METHOD: Between February 1999 and March 2001 we performed 131 LT with 121 cadaveric donors in our unit. Ten domino LTs were performed. RESULTS: Patients with FAP were younger (37 years) than recipients of the second LT (64 years). The evolution of patients undergoing transplantation for FAP was excellent and all are currently alive and without complications. Among recipients of the second LT, one patient died in the postoperative period. A further two patients died from tumoral recurrence and hepatitis C virus recurrence 18 months and 9 months after transplantation, respectively. The remaining patients have shown no symptoms of FAP during the follow-up. CONCLUSION: The results of this study show that domino LT is technically feasible. The technique increases the number of grafts without apparent risk either to the recipient with FAP or to the recipient of the latter's explanted liver.

Risk factors for development of de novo neoplasia after liver transplantation.

Liver transplant recipients are at greater risk for de novo neoplasia, especially lymphoma and nonmelanoma skin cancer; however, risk factors for this complication have not been well studied. Clinical and pathological records of 137 consecutive liver transplant recipients who had survived for at least 1 year were reviewed to register de novo neoplasia. Ten variables were analyzed for their association with the development of de novo malignancies by means of a log-rank test and stepwise selection in a multivariate analysis using the Cox proportional hazard model. Thirty de novo neoplasias appeared in 22 of 137 transplant recipients between 12 and 104 months after orthotopic liver transplantation (OLT; median follow-up, 69 months): 14 patients had 21 skin cancers, 6 patients had solid-organ cancer, and 3 patients developed a lymphoproliferative disease. Probabilities of de novo neoplasia were 13% at 5 years post-OLT and 26% at 8 years post-OLT. The only associated risk factor for any neoplasia was age. Age and hepatocarcinoma were independent risk factors associated with skin cancer. That hepatocarcinoma in the explanted liver is an independent risk factor for skin cancer suggests there is individual susceptibility to both neoplasias.

Influence of donor post-reperfusion changes on graft evolution after liver transplant.

INTRODUCTION: The increase in indications for liver transplantation has meant that waiting lists are growing ever longer. For this reason, broadening the donor pool is a priority for most groups. OBJECTIVE: The objective of this study was to analyze the predictive value of post-reperfusion biopsy in the evolution of graft function after liver transplantation. PATIENTS: One hundred and forty-eight liver biopsies, obtained after graft reperfusion, were analyzed. Eight pathological variables and thirty-seven clinical variables of the donors were recorded. Risk factors for presenting primary graft non-function or dysfunction were studied with logistic regression models. Factors associated to the long-term graft failure were studied using Cox analysis and actuarial survival curves. RESULTS: Microvesicular steatosis greater than 50% was the only risk factor associated to graft dysfunction in the multivariate logistic regression model. Microvesicular steatosis greater than 30%, severe hepatocyte necrosis and presence of abundant neutrophilic leukocytes were risk factors associated to graft failure in the univariate study. Only steatosis remained as an independent risk factor in the multivariate study. These grafts also presented poorer long-term survival. Abundant polymorphonuclear infiltrate was associated to a higher frequency of biliary complications. CONCLUSIONS: Microvesicular steatosis implies a better evolution than macrovesicular steatosis. Neutrophilic infiltrate and hepatocellular necrosis lead to poorer initial graft function and reduced long-term survival.

The impact of donor age on liver transplantation: influence of donor age on early liver function and on subsequent patient and graft survival.

BACKGROUND: The urgent need to increase the organ donor pool has led to the expansion of criteria for donor selection. The aim of this study was to analyze the influence of donor age on early graft function, subsequent graft loss, and mortality after liver transplantation (LT). METHODS: Data on LT were evaluated retrospectively in a population-based cohort of 400 LTs in 348 patients. Of these, 21 (5%) were from donors >70 years old. Pretransplantation donor and recipient characteristics and the evolution of recipients were analyzed. The influence of donor age as a risk factor was assessed using univariate and multivariate analyses. RESULTS: Actuarial graft survival was 89% at 1 month after LT, 81% after 6 months, and 59% after 60 months. Multivariate analysis demonstrated that only donor age (>70 years old) was associated with a higher risk of long-term graft loss (relative risk [RR]=1.4, 95% confidence interval [CI]=1-1.9; P=0.03) and mortality (RR=1.7, 95% CI=1.2-2.3; P=0.01). Graft survival of septuagenarian livers was 80% at 1 month after LT, 56% after 6 months, and 25% after 54 months. Actuarial survival analysis (Kaplan-Meier curves) also demonstrated worse evolution in recipients of livers from old donors (log-rank test, P<0.001). CONCLUSIONS: Advanced donor age is associated with lower graft and recipient survival.

Postreperfusion biopsies are useful in predicting complications after liver transplantation.

Biliary complications after orthotopic liver transplantation (OLT) may occur because of preservation injury (PI). In this study, we examine findings on routine reperfusion biopsy specimens in relation to the occurrence of biliary complications and graft outcome. From 1997 to 2000, a total of 193 OLTs were performed in our center. Postreperfusion biopsy specimens were analyzed and histological lesions were graded. For analysis, grafts were grouped into 2 categories: the presence or absence of PI (severe to moderate lesions versus mild or no lesions). Histological evidence of PI was present in 17% of the biopsy specimens. The incidence of grafts with PI and ischemia time longer than 12 hours was 38% compared with 14% in PI and short ischemia time (P =.02). Biliary complications were also more frequent in the PI group (28% v 14%; P =.03). Study of risk factors by means of logistic regression analysis confirmed that the PI group had a greater risk for biliary complications (relative risk, 2.8; 95% confidence interval, 1 to 7.4; P =.03). Moreover, moderate macrovesicular steatosis was found in 6% of the grafts, resulting in a 40% graft loss rate. We found that an increased presence of neutrophilic infiltrates in the postreperfusion biopsy specimen, indicating PI, was related to an increased incidence of biliary complications. Moreover, moderate macrovesicular steatosis was associated with increased graft loss. Therefore, postreperfusion biopsies are useful in anticipating post-OLT complications.

Complications of thoracentesis in cirrhotic patients with pleural effusion.

OBJECTIVE: To study the complications of thoracentesis, either diagnostic or therapeutic, in cirrhotic patients with pleural effusion. EXPERIMENTAL DESIGN: A cohort prospective study. A diagnostic thoracentesis was performed at admission or when spontaneous bacterial empyema was suspected; a therapeutic thoracentesis was conducted in patients with dyspnea that did not improve with medical treatment. A chest radiography and a careful clinical follow up were performed in all patients within 24 hours after the procedure. We studied the risk factors for developing pneumothorax and the actuarial probability of pneumothorax after consecutive therapeutic thoracentesis. PATIENTS: All cirrhotic patients admitted with pleural effusion over a 4-year period. The study included 69 patients. RESULTS: During the study period, we performed 245 thoracentesis, 150 diagnostic and 95 therapeutic ones. The most severe complication was pneumothorax in 10 cases (4%), after 2 out of 150 (1.3%) diagnostic thoracentesis and after 8 out of 95 (8.4%) therapeutic thoracentesis (RR, 95% CI 6.8, 1.41-32.77, p < 0.01). The actuarial risk of pneumothorax after the first, second and fourth therapeutic thoracentesis was 7.7%, 25.3% and 34.7%, respectively. CONCLUSIONS: Diagnostic thoracentesis in cirrhotic patients is associated to a low morbidity. Therapeutic thoracentesis is a risk factor for pneumothorax and the risk increases after consecutive thoracentesis. A chest radiograph is not justified after a diagnostic thoracentesis, but should be done after a therapeutic thoracentesis.

[Analysis of 500 liver transplantations at Bellvitge Hospital, Spain]. / Análisis de 500 trasplantes hepáticos en el Hospital de Bellvitge.

BACKGROUND: We present the experience of the liver transplantation program at the Hospital of Bellvitge with 500 transplantations performed during 15 years, to describe changes in liver transplantation observed throughout the time and to analyze the long term results. PATIENTS AND METHOD: Five groups each one including 100 consecutive transplantations are studied. RESULTS: The main indications were hepatocellular carcinoma (23%), alcoholic cirrhosis (22.8%), and post-hepatitis C cirrhosis (18.8%). Sixty-five retransplantations were performed in 59 patients (13%), being the more frequent indications arterial thrombosis (13 patients) and primary nonfunction of graft (10 patients). In 10 patients a hepatorenal transplantation was performed. In group I, the most frequent donor cause of death was cranial traumatism (80%), while in group V it was the vascular pathology (52%). There were other significative differences between these groups of patients (I vs V): patients with stage 2 or 3 from UNOS status (45 vs 19%), blood use (29.6 [26] vs 4.6 [5.3] PRBC), ICU stay (13 [13] vs 7.4 [11] days), hospital stay (40 [52] vs 23.7 [17] days), rejection rate (46 vs 20%) and primary graft nonfunction (9 vs 3%). However, the infection rates (48 vs 54.5%) and biliary tract complications (26 vs 20%) have not shown statistically significant differences. Actuarial one and 5-year survival are 83 and 70% respectively. CONCLUSIONS: An important and progressive improvement of liver transplantation results has been observed. However, de novo tumours, hepatitis C virus recurrence and chronic rejection can limit long term results.

Influence of the vitamin D receptor gene polymorphism on bone loss in men after liver transplantation.

BACKGROUND: Bone loss is a frequent complication after liver transplantation. OBJECTIVE: To investigate whether vitamin D receptor gene polymorphism influences bone loss in men after liver transplantation. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS: 55 male candidates for liver transplantation. MEASUREMENTS: Lumbar spine bone mineral density was measured before and 3, 6, 12, and 24 months after liver transplantation. Vitamin D receptor genotype was determined by restriction endonuclease Bsml. RESULTS: Vitamin D receptor genotypes were significantly associated with post-transplantation changes in bone mineral density (P = 0.028). Within 3 months after transplantation, patients with the genotypes Bb or BB showed a vertebral bone loss substantially greater than that in patients with the bb genotype (between-group difference in the percentage change with respect to baseline bone mineral density, 3.7% [95% CI, 0.6% to 6.9%1). In 3 to 24 months after transplantation, bone mineral density increased steadily in the three allelic groups. CONCLUSIONS: Vitamin D receptor gene polymorphism influences bone loss after liver transplantation. Patients with the bb genotype are, to some extent, protected against post-transplantation bone loss.

[Is surgery for portal hypertension a contraindication for liver transplantation?]. / Representa la cirugía de la hipertensión portal una contraindicación al trasplante hepático?

INTRODUCTION: Orthotopic liver transplantation (OLT) is the only curative treatment for hepatic cirrhosis and is the most effective in the control of portal hypertension. The aim of this study was to analyze whether greater morbi-mortality is observed in patients undergoing liver transplantation with previous surgery for portal hypertension with respect to patients not having undergone this surgery. MATERIALS AND METHODS: Different variables were analyzed in 2 groups of transplanted patients: one of 18 patients who had previously undergone surgery for portal hypertension and another group of 54 patients without this previous surgery. RESULTS: The following factors were studied: mean operative time and length of anahepatic phase, intraoperative consumption of concentrates of erythrocytes, fresh frozen plasma, units of platelets and cryoprecipitates, days of mechanical ventilation, stay in the ICU and total postoperative stay. No significant differences were observed (p < 0.05) in any of these factors or in survival. DISCUSSION: On analysis of the difficulty of surgical technique, postoperative evolution and survival and based on the variables described it may be concluded that previous surgery for portal hypertension does not only not contraindicate posterior liver transplantation, but rather may be useful in patients with an adequate hepative reserve presenting variceal hemorrhage since posterior transplantation does not present a worsened prognosis.

[Resection as elective treatment of hilar cholangiocarcinoma (Klatskin tumor)]. / La resección como tratamiento de elección del colangiocarcinoma hiliar (tumor de Klatskin).

A retrospective analysis of our experience in the treatment of hiliary cholangiocarcinoma or Klatskin tumor was performed with the aim of evaluating the morbi-mortality and prognosis of its treatment to thereby determine the usefulness of the different therapeutic options. From 1989 to 1997, 51 patients diagnosed with hiliary cholangiocarcinoma were treated in our hospital. Surgery was indicated in 16 with curative aims (group I) while palliative treatment with percutaneous biliary drainage was indicated in 35 (group II). Biliary resection was carried out in 8 patients being associated with hepatic resection in 4 (group IA) and in 8 patients undergoing liver transplantation (group IB). Clinico-epidemiologic data and hospital stay were similar in all the groups. The frequency of complications was similar in groups I and II although the frequency of cholangitis (49%) in group II was noticeable. The percentage of readmissions was also greater in group II (12 vs 46%, respectively; p = 0.03) with prosthesis obstruction being the most frequent cause. Accumulated survival at 1, 2, and 3 years in group I was 84, 64 and 48% with a median survival of 33 months, while in group II the median survival was of 6 months with no patient surviving more than 2 years (p = 0.0001). When groups IA and IB were compared, greater frequency of complications in groups IA (100 vs 37%; p = 0.002), similar frequency of readmissions (87 vs 75%; p = NS), median survival greater in group IB (12.5 months vs 48 months) and significantly higher actuarial survival in group IB (48% in 2 years vs 83% to 2 years; p = 0.02) was observed. In conclusion, surgery is the treatment of choice in hiliary cholangiocarcinoma whenever possible, given the greater survival without a significant increase in morbimortality. Likewise, we consider that liver transplantation is a useful option in the treatment of patients with cholangiocarcinoma type IV of Bismuth.