Xavier Xiol

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.

Risk factors for resistance to ceftriaxone and its impact on mortality in community, healthcare and nosocomial spontaneous bacterial peritonitis

BACKGROUND & AIMS The recent emergence of third-generation cephalosporin resistance in spontaneous bacterial peritonitis is of great concern, although neither the risk factors for resistance nor its real impact on mortality have been well defined. METHODS We conducted a retrospective study of all spontaneous bacterial peritonitis episodes with positive blood and/or ascitic culture at our center (2001-2009). Episodes were classified according to the place of acquisition: community, healthcare system, or nosocomial. RESULTS Two hundred and forty-six episodes were analyzed in 200 patients (150 males, 57.3 years): 34.6% community-acquired, 38.6% healthcare system-acquired, and 26.8% nosocomially-acquired. Third-generation cephalosporin resistance occurred in 21.5% (7.1% community-acquired, 21.1% healthcare system-acquired, 40.9% nosocomially-acquired). These resistant cases were categorized as extended-spectrum β-lactamase-producing Gram-negative bacilli, other resistant Gram-negative bacilli, and Enterococci. Risk factors for resistance were previous use of cephalosporins, diabetes mellitus, upper gastrointestinal bleeding, nosocomial acquisition, and a low polymorphonuclear count in ascites. Regarding third-generation cephalosporin resistance, adequate empirical treatment was 80.7%. Independent predictors of mortality were nosocomial acquisition, poor hepato-renal function, immunosuppressive therapy, a marked inflammatory response during the episode and either third-generation cephalosporin-resistance or low rates of adequate empirical treatment. CONCLUSIONS The risk of third-generation cephalosporin resistance was particularly high in nosocomially-acquired episodes of spontaneous bacterial peritonitis, but also occurred in healthcare system-acquired cases. The extent of resistance and the adequacy of empirical antibiotics had a significant effect on mortality along with the patients hepato-renal function. These data can help determine the most suitable empirical antimicrobial treatments in these patients.

Secondary bacterial peritonitis in cirrhosis: A retrospective study of clinical and analytical characteristics, diagnosis and management

BACKGROUND & AIMS Secondary bacterial peritonitis in cirrhotic patients is an uncommon entity that has been little reported. Our aim is to analyse the frequency, clinical characteristics, treatment and prognosis of patients with secondary peritonitis in comparison to those of patients with spontaneous bacterial peritonitis (SBP). METHODS Retrospective analysis of 24 cirrhotic patients with secondary peritonitis compared with 106 SBP episodes. RESULTS Secondary peritonitis represented 4.5% of all peritonitis in cirrhotic patients. Patients with secondary peritonitis showed a significantly more severe local inflammatory response than patients with SBP. Considering diagnosis of secondary peritonitis, the sensitivity of Runyons criteria was 66.6% and specificity 89.7%, Runyons criteria and/or polymicrobial ascitic fluid culture were present in 95.6%, and abdominal computed tomography was diagnostic in 85% of patients in whom diagnosis was confirmed by surgery or autopsy. Mortality during hospitalization was higher in patients with secondary peritonitis than in those with SBP (16/24, 66.6% vs. 28/106, 26.4%) (p<0.001). There was a trend to lower mortality in secondary peritonitis patients who underwent surgery (7/13, 53.8%) than in those who received medical treatment only (9/11, 81.8%) (p=0.21). Considering surgically treated patients, the time between diagnostic paracentesis and surgery was shorter in survivors than in non-survivors (3.2+/-2.4 vs. 7.2+/-6.1 days, p=0.31). CONCLUSIONS Secondary peritonitis is an infrequent complication in cirrhotic patients but mortality is high. A low threshold of suspicion on the basis of Runyons criteria and microbiological data, together with an aggressive approach that includes prompt abdominal computed tomography and early surgical evaluation, could improve prognosis in these patients.

Risk of transmission of systemic transthyretin amyloidosis after domino liver transplantation

Recent reports of the transmission of systemic transthyretin (TTR) amyloidosis after domino liver transplantation (DLT) using grafts from patients with familial amyloid polyneuropathy (FAP) have raised concerns about the procedure. The aim of this study was to evaluate the transmission incidence of systemic TTR amyloidosis after DLT with a complete clinical, neurological, and pathological assessment. At our institution, DLT has been performed 31 times with livers from patients with FAP. Seventeen of the 19 patients still alive in 2008 agreed to enter the study. This cross‐sectional study of this cohort of patients included clinical assessments, rectal biopsy, and electroneuromyography (as well as sural nerve biopsy when it was indicated). The mean follow‐up at the time of the study was 62.6 ± 2.9 months. Clinically, 3 patients complained of weak dysesthesia. When a focused study was performed, 8 patients reported some kind of neurological and/or gastrointestinal disturbance. Six of the rectal biopsy samples showed amyloid deposits (TTR‐positive). Electromyography (EMG) showed signs of mild sensorimotor neuropathy in 3 cases and moderate to severe sensorimotor neuropathy in 1 case. Only 2 of the 4 patients with EMG signs of polyneuropathy showed amyloid deposits in their rectal biopsy samples. Sural nerve biopsy revealed amyloid deposits (TTR‐positive) in all 4 patients with EMG signs of polyneuropathy. Two patients with normal EMG findings had TTR‐positive amyloid deposits in their sural nerve biopsy samples. In conclusion, de novo systemic amyloidosis after DLT may be more frequent and appear earlier than was initially thought. In our opinion, however, the graft shortage still justifies DLT in selected patients, despite the risk of de novo systemic amyloidosis. Sural nerve biopsy with EMG and clinical correlation is mandatory for confirming the disease. Indeed, other causes of neuropathy should be excluded. Liver Transpl 16:1386–1392, 2010.

Impact of immunosuppression without steroids on rejection and hepatitis C virus evolution after liver transplantation: Results of a prospective randomized study

The purpose of this study was to evaluate the influence of a steroid‐free immunosuppression on hepatitis C virus (HCV) recurrence. A total of 198 liver transplantation (LT) patients were randomized to receive immunosuppression with basiliximab and cyclosporine, either with prednisone (steroid [St] group) or without prednisone (no steroids [NoSt] group). The group of 89 HCV‐infected patients was followed up with protocol biopsies for 2 years after LT. This group of HCV patients are the patients evaluated in the present study. The rejection rate was 19% (St: 21% versus NoSt: 17%; P = 0.67). Patients in the St group had a slightly higher rate of bacterial infections (59% versus 38%; P = 0.05). Almost all patients had histological HCV‐recurrence (St: 39/40 (97%) versus NoSt: 40/41 (97%); P = 1). The percentage of accumulated biopsies with grade 4 portal inflammation at 6 months, 1 year, and 2 years were, 23%, 49%, and 49% in the NoSt group, compared to 33%, 55%, and 69% in the St group, respectively (P = 0.04 at 2 years). The percentage of accumulated biopsies with grade 3 or 4 fibrosis at 6 months, 1 year, and 2 years were 0%, 8%, and 22% in the NoSt group, compared to 8%, 19%, and 31% in the St group, respectively. Immunosuppression without steroids in HCV patients is safe, reduces bacterial infections and metabolic complications, and improves histological short‐term evolution of HCV recurrence. Liver Transpl 14:1752–1760, 2008.

Low complement levels and opsonic activity in hepatic hydrothorax: its relationship with spontaneous bacterial empyema.

Goals To analyze the pleural fluid factors that might cause spontaneous bacterial empyema (SBEM) in patients with cirrhotic hydrothorax. Background Pathogenic mechanism of SBEM of cirrhotic patients is probably similar to that of spontaneous bacterial peritonitis, but local factors affecting pleural fluid have not been studied. Study Determination of C3, C4, and opsonic activity levels of pleural fluid in a cohort of patients with pleural effusions of different causes. Results Forty-eight patients had hepatic hydrothorax; 8, heart failure and 45, exudates (9, tuberculosis; 21, malignancies; 10, other). Of the 48 cirrhotic patients, 15 developed SBEM on admission. The pleural fluid of cirrhotic patients showed significantly lower levels of total protein, complement, and opsonic activity than did the fluids of patients with other causes of SBEM. Patients who developed SBEM had lower concentrations of pleural fluid total protein and C3 and had a higher Child–Pugh score than patients who did not develop the infection. Conclusion Cirrhotic patients with hepatic hydrothorax have lower pleural fluid opsonic activity and C3 levels than those found in the pleural fluid of patients with other causes. Patients who develop SBEM have lower levels of pleural fluid C3, pleural fluid total protein, and a higher Child–Pugh score than those who do not develop SBEM.

Liver transplantation in patients with hepatic hydrothorax

Hepatic hydrothorax is a uncommon complication of cirrhotic patients and the results of liver transplantation (OLT) in patients with this complication are not well defined. We studied postoperative complications and survival of 28 patients with hepatic hydrothorax transplanted at our center during a period of 12 years, comparing them with a control group of 56 patients transplanted immediately before and after each case. There were no differences between hydrothorax group and control group in days of mechanical ventilation after surgery, transfusion requirements, postoperative mortality and long‐term survival (70% vs. 55% at 8 years, P = 0.11). Long‐term evolution was similar between patients with refractory hepatic hydrothorax or spontaneous bacterial empyema and those with noncomplicated hepatic hydrothorax. Hepatic transplantation is an excellent therapeutic option for patients with hepatic hydrothorax. Presence of hepatic hydrothorax does not imply more postoperative complications, and long‐term survival is similar to other indications of hepatic cirrhosis.

Paracetamol in therapeutic dosages and acute liver injury: causality assessment in a prospective case series

BackgroundAcute liver injury (ALI) induced by paracetamol overdose is a well known cause of emergency hospital admission and death. However, there is debate regarding the risk of ALI after therapeutic dosages of the drug.The aim is to describe the characteristics of patients admitted to hospital with jaundice who had previous exposure to therapeutic doses of paracetamol. An assessment of the causality role of paracetamol was performed in each case.MethodsBased on the evaluation of prospectively gathered cases of ALI with detailed clinical information, thirty-two cases of ALI in non-alcoholic patients exposed to therapeutic doses of paracetamol were identified. Two authors assessed all drug exposures by using the CIOMS/RUCAM scale. Each case was classified into one of five categories based on the causality score for paracetamol.ResultsIn four cases the role of paracetamol was judged to be unrelated, in two unlikely, and these were excluded from evaluation. In seven of the remaining 26 cases, the RUCAM score associated with paracetamol was higher than that associated with other concomitant medications. The estimated incidence of ALI related to the use of paracetamol in therapeutic dosages was 0.4 per million inhabitants older than 15 years of age and per year (99%CI, 0.2-0.8) and of 10 per million paracetamol users-year (95% CI 4.3-19.4).ConclusionsOur results indicate that paracetamol in therapeutic dosages may be considered in the causality assessment in non-alcoholic patients with liver injury, even if the estimated incidence of ALI related to paracetamol appears to be low.

Use of reagent strips for the rapid diagnosis of spontaneous bacterial empyema.

Goals: To assess the utility of reagent strips for rapid diagnosis of spontaneous bacterial empyema in cirrhotic patients with hepatic hydrothorax. Background: Analysis of ascitic fluid using reagent strips is a useful diagnostic test for spontaneous bacterial peritonitis. Methods: A reagent strip for leukocyte esterase designed for the testing of urine was used to evaluate pleural fluid analysis in 47 nonselected thoracenteses in 28 cirrhotic patients with hepatic hydrothorax. Results: Twelve spontaneous bacterial empyemas were diagnosed. Simultaneous spontaneous bacterial peritonitis was present in 7 of 10 cases in which ascites fluid was analyzed. When a test result of 3 or 4 was considered positive, sensitivity was 83% (10 of 12), specificity was 100% (35 of 35), and positive predictive value was 100%. When result of 2 or more was considered positive, sensitivity was 92% (11 of 12), specificity was 80% (28 of 35), and negative predictive value was 97%. Conclusion: Analysis of pleural fluid with reagent strips is a rapid, easy to use, and inexpensive tool for the diagnosis of spontaneous bacterial empyema in cirrhotic patients. A positive result should be considered an indication for antibiotic therapy.

External validation of a prognostic model for predicting survival of cirrhotic patients with refractory ascites

OBJECTIVE:Cirrhotic patients with refractory ascites (RA) have a poor prognosis, although individual survival varies greatly. A model that could predict survival for patients with RA would be helpful in planning treatment. Moreover, in cases of potential liver transplantation, a model of these characteristics would provide the bases for establishing priorities of organ allocation and the selection of patients for a living donor graft. Recently, we developed a model to predict survival of patients with RA. The aim of this study was to establish its generalizability for predicting the survival of patients with RA.METHODS:The model was validated by assessing its performance in an external cohort of patients with RA included in a multicenter, randomized, controlled trial that compared large-volume paracentesis and peritoneovenous shunt. The values for actual and model-predicted survival of three risk groups of patients, established according to the model, were compared graphically and by means of the one-sample log-rank test.RESULTS:The model provided a very good fit to the survival data of the three risk groups in the validation cohort. We also found good agreement between the survival predicted from the model and the observed survival when patients treated with peritoneovenous shunt and with paracentesis were considered separately.CONCLUSION:Our survival model can be used to predict the survival of patients with RA and may be a useful tool in clinical decision making, especially in deciding priority for liver transplantation.