Mortality Analysis of Acute Liver Failure in Uruguay.

BACKGROUND: Acute liver failure (ALF) is a syndrome with high mortality. OBJECTIVE: Describe characteristics and outcomes of patients with ALF in Uruguay, and identify factors associated with mortality. METHODS: A retrospective analysis of 33 patients with ALF was performed between 2009 and 2017. RESULTS: The patients' median age was 43 years, and 64% were women. Average Model for End-Stage Liver Disease (MELD) score at admission was 33. The median referral time to the liver transplant (LT) center was 7 days. The most common etiologies were viral hepatitis (27%), indeterminate (21%), autoimmune (18%), and Wilson disease (15%). Overall mortality was 52% (71% of transplanted and 46% of nontransplanted patients). Dead patients had higher referral time (10 vs 4 days, P = .008), higher MELD scores at admission (37 vs 28) and highest achieved MELD scores (42 vs 29; P < .001), and higher encephalopathy grade III to IV (94% vs 25%, P < .001) than survivors. Patients without LT criteria (n = 4) had lower MELD score at admission (25 vs 34, P = .001) and highest achieved MELD score (27 vs 37, P = .008) compared with the others. Patients with LT criteria but contraindications (n = 7) had higher MELD scores at admission (38 vs 31, P = .02), highest achieved MELD scores (41 vs 34, P = .03), and longer referral time (10 days) than those without contraindications (3.5 days) or those without LT criteria (7.5 days, P = .02). Twenty-two patients were listed; LT was performed in 7, with a median time on waiting list of 6 days. CONCLUSIONS: ALF in Uruguay has high mortality associated with delayed referral to the LT center, MELD score, and encephalopathy. The long waiting times to transplantation might influence mortality.

Risk Factors of Mortality After Liver Transplantation in Uruguay.

INTRODUCTION: Identification of predictive factors of mortality in a liver transplant (LT) program optimizes patient selection and allocation of organs. OBJECTIVE: To determine survival rates and predictive factors of mortality after LT in the National Liver Transplant Program of Uruguay. METHODS: A retrospective study was conducted analyzing data prospectively collected into a multidisciplinary database. All patients transplanted since the beginning of the program on July 2009 to April 2017 were included (n = 148). Twenty-nine factors were analyzed through the univariate Kaplan-Meier model. A Cox regression model was used in the multivariate analysis to identify the independent prognostic factors for survival. RESULTS: Overall survival was 92%, 87%, and 78% at discharge, 1 year, and 3 years, respectively. The Kaplan-Meier survival curves were significantly lower in: recipients aged >60 years, Model for End-Stage Liver Disease score >21, LT due to hepatocellular carcinoma (HCC) and acute liver failure (ALF), donors with comorbidities, intraoperative blood loss beyond the median (>2350 mL), red blood cell transfusion requirement beyond the median (>1254 mL), intraoperative complications, delay of extubation, invasive bacterial, and fungal infection after LT and stay in critical care unit >4 days. The Cox regression model (likelihood ratio test, P = 1.976 e-06) identified the following independent prognostic factors for survival: LT for HCC (hazard ratio [HR] 4.511; P = .001) and ALF (HR 6.346; P = .004), donors with comorbidities (HR 2.354; P = .041), intraoperative complications (HR 2.707; P = .027), and invasive fungal infections (HR 3.281; P = .025). CONCLUSION: The survival rates of LT patients as well as the mortality-associated factors are similar to those reported in the international literature.

Impact of a Multimodal Approach in Prevention of Surgical Site Infection in Hepatic Transplant Recipients.

INTRODUCTION: In liver transplant (LT) recipients, surgical site infection (SSI) represents an important cause of morbidity and mortality. OBJECTIVE: This study measures the impact of a multimodal approach to the incidence of surgical site infection in LT recipients. MATERIALS AND METHODS: All of the LT recipients in our department were registered on the national database in solid organ transplant. A study was performed in two analytical-interventional phases. Phase 1 took place between July 14, 2009, and February 20, 2014. Phase 2 took place between February 21, 2014, and July 15, 2015. The multimodal change implemented during phase 1 was that 0.5% alcoholic chlorhexidine and ether were applied to the surgical field; surgical prophylaxis was primarily with ampicillin/sulbactam plus cefazolin. In phase 2, 2% alcoholic chlorhexidine alone was applied to the surgical field. The prior standard prophylaxis was changed to piperacillin tazobactam administered during surgery as a continuous infusion of 13.5 g over 8 hours with a pre-incision loading dose of 4.5 g. The loading dose of piperacillin tazobactam was combined with a single dose of gentamicin of 5 mg/kg. RESULTS: One hundred eight patients have received transplants since the start of the program: 82 patients during phase one and 26 patients during phase two. During phase 1, 13 cases of SSI were recorded, representing a rate of 15.85 per 100 transplants. Sixteen micro-organisms were isolated during phase 1, of which 12 corresponded to gram-negative bacilli. With regard to resistance profiles, 13 showed multidrug resistant and extensively drug resistant profiles. During phase 2, no cases of SSI were recorded (relative risk = 0.158 [95% confidence interval 0.0873-0.255], P = .0352]. CONCLUSION: A multimodal approach allowed for the reduction of the incidence of SSI in LTs and offered a protective strategy.

Toxoplasma gondii pneumonia in liver transplantation: survival after a severe case of reactivation.

Toxoplasmosis is an infrequent infection in solid organ transplantation, except in heart transplantation, where the grafting of a positive organ in a negative recipient transmits the infection in a high percentage of cases, in the absence of prophylaxis. We report a case of pneumonia by Toxoplasma gondii in a woman who received a liver transplant and had pre-transplant positive serology. Diagnosis was made by cytologic examination of bronchoalveolar lavage fluid, where the parasite was observed with hematoxylin-eosin and Giemsa staining. That finding was confirmed by direct immunofluorescence and positive polymerase chain reaction. The patient had a favorable outcome, although she had not initially received first-choice drugs. This was a case of severe illness secondary to reactivation of Toxoplasma infection, diagnosed pre-mortem and with a favorable outcome. Duration of treatment and need for secondary prophylaxis in these patients are discussed in the literature. Although infrequent, toxoplasmosis must be considered among the differential diagnoses of pulmonary infiltrates in solid organ transplantation.

Von Willebrand factor could be an index of endothelial dysfunction in patients with cirrhosis: relationship to degree of liver failure and nitric oxide levels.

BACKGROUND/AIMS: The aim of this study was to evaluate the relationship between plasma levels of von Willebrand factor (vWF), a marker of endothelial cell activation, and nitric oxide, a powerful vasodilator synthesized by endothelial cells, in 27 patients with cirrhosis at different stages of the disease. These results were compared with those of age-matched normal, healthy subjects (n=10). METHODS: vWF:antigen was measured by electro-immunodiffusion test and serum nitrite and nitrate levels, the stable end products of nitric oxide metabolism, were determined by an enzymatic procedure. RESULTS: vWF:antigen and nitrite/nitrate levels were significantly higher in cirrhotic patients (367+/-185% and 29.3+/-10.8 micromol/l) than in healthy subjects (92+/-20% and 19.2+/-8.3 micromol/l, p<0.05, respectively). Higher levels of vWF:antigen and nitrites/nitrates were observed in patients with more advanced degrees of liver failure, as reflected by quantitative Child-Pugh's score (516+/-154% and 38.3+/-7.8 micromol/l in Child-Pugh > or = 9 vs 227+/-61% and 21.0+/-6.1 micromol/l in Child-Pugh <9, p<0.001, respectively). Moreover, both endothelial-related factors were higher in patients with ascites than those without ascites (543+/-158% and 37.8+/-8.9 micromol/l vs 262+/-103% and 24.4+/-8.8 micromol/l, p<0.001, respectively). In the overall series, a highly significant linear correlation between nitrites/nitrates and vWF:antigen levels was observed in patients with cirrhosis (r=0.79, p<0.001). CONCLUSIONS: These results support a cirrhosis-related endothelial dysfunction and suggest that plasma vWF measurement could be useful as a marker of endothelial disturbance in patients with cirrhosis.

Splanchnic hyperemia after liver transplantation in patients with end-stage liver disease.

Systemic and splanchnic hemodynamic parameters were evaluated in 12 patients with cirrhosis before and 3 and 6 months after liver transplantation. Results were compared with those obtained in 8 healthy subjects. Three months after liver transplantation recipients had an increase in mean arterial pressure (98 +/- 7 v 78 +/- 9 mmHg; P < .05), an insignificant decrease in cardiac index (3. 4 +/- 0.6 v 4.0 +/- 1.0 L . min-1 . m-2), and a marked increase in peripheral vascular resistance (1,563 +/- 308 v 800 +/- 205 dyne . s . cm-5; P < .05) compared with pretransplantation values. Portal blood flow was also significantly increased (1,494 +/- 200 v 829 +/- 130 mL/min; P < .05). These hemodynamic changes were more pronounced 6 months after transplantation (mean arterial pressure, 100 +/- 8 mmHg; cardiac index, 3.0 +/- 1.0 L . min-1 . m-2; P < .01; peripheral vascular resistance, 1,680 +/- 405 dyne . s . cm-5; portal blood flow, 1,520 +/- 180 mL/min). Systemic hemodynamics 6 months after liver transplantation were similar to those observed in the healthy control group (mean arterial pressure, 95 +/- 6 mmHg; cardiac index, 2.9 +/- 0.9 L . min-1 . m-2; peripheral vascular resistance, 1,480 +/- 380 dyne . s . cm-5). However, portal blood flow was still significantly higher than in healthy controls at 6 months (1,520 +/- 180 v 910 +/- 140 mL/min; P < .05). This study shows that systemic hemodynamics are normalized after liver transplantation. However, an increase in portal blood flow occurs and persists for at least 6 months after liver transplantation. Further studies are needed to clarify the cause of the abnormally high portal flows.

Daily variation in portal blood flow and the effect of propranolol administration in a randomized study of patients with cirrhosis.

A nocturnal increase in portal pressure and blood flow was demonstrated in patients with cirrhosis, suggesting that these hemodynamic changes may contribute to the triggering of the hemorrhagic episodes observed during the night in these patients. It is known that propranolol reduces portal flow, thus reducing the risk of variceal bleeding. In a double-blind, placebo-controlled study, we evaluated the effect of long-term propranolol administration on the daily fluctuation of systemic and splanchnic hemodynamic parameters in 14 patients with cirrhosis. Cardiac output and portal blood flow were measured by the Doppler technique. A daily fluctuation of both cardiac output and portal blood flow was observed, peaking at midnight. beta-Adrenergic blockade was manifested by a significant reduction in heart rate (-21% +/- 4%, P < .01) and cardiac output (-12% +/- 2%, P < .05). A significant decrease in portal blood flow (-20% +/- 4%, P < .01) was also observed in these patients. Propranolol administration blunted the time-related changes in cardiac output and portal blood flow. In contrast, patients receiving placebo had a nocturnal peak of both parameters similar to that observed under basal conditions. Our study shows that chronic propranolol administration abolishes the nocturnal peak of portal blood flow in patients with cirrhosis and indicates a preventive effect of propranolol in these patients.

Pentoxifylline, a drug with rheological effects, decreases portal pressure in an experimental model of cirrhosis.

OBJECTIVE: To evaluate the influences of blood viscosity changes, mediated by a haemorheological agent, on splanchnic and systemic haemodynamic parameters in rats with cirrhosis due to chronic bile duct ligation. METHODS: Blood viscosity was measured using a cone-plate viscometer and whole blood filterability was determined by a filtration method. Cardiac index and portal venous inflow were measured using radioactive microspheres. Measurements were performed 30 min after double-blind administration of placebo or pentoxifylline (25 mg/kg, intravenously). RESULTS: As compared with placebo, pentoxifylline-treated cirrhotic rats had a lower portal pressure (13.8 +/- 1.4 vs. 12.1 +/- 1.6 mmHg, P < 0.05) and blood viscosity at shear rates of 115/s (6.6 +/- 0.8 vs. 5.8 +/- 0.3 mPas, P < 0.05), associated with an improvement of whole blood filterability (45.0 +/- 12.9 vs. 20.0 = 3.9 s/ml, P < 0.01). Similar values of mean arterial pressure, cardiac index and portal venous inflow were observed in both groups. A significant correlation was found between portal pressure and blood viscosity at a shear rate of 115/s (r = 0.71, P < 0.01). CONCLUSION: These results suggest that portal pressure can be modified by pentoxifylline in an experimental model of cirrhosis. These haemodynamic changes are associated with a lower blood viscosity and whole blood filterability. Pentoxifylline may be a new approach in the treatment of portal hypertension.

[Renal failure in patients with liver transplant: incidence and predisposing factors]. / Insuficiencia renal en pacientes con trasplante hepático: incidencia y factores predisponentes.

Renal failure is a common finding in patients undergoing orthotopic liver transplantation. The aim of the present study was to evaluate the incidence, prognostic value of pre, intra and postoperative factors and severity of renal dysfunction in patients who undergo liver transplantation. Therefore, the records of 38 consecutive adult patients were reviewed. Renal failure was defined arbitrarily as an increase in creatinine (> 1.5 mg/dl) and/or blood urea (> 80 mg/dl). Three patients were excluded of the final analysis (1 acute liver failure and 2 with a survival lower than 72 hs.) Twenty one of the 35 patients has renal failure after orthotopic liver transplantation. Six of these episodes developed early, having occurred within the first 6 days. Late renal impairment occurred in 15 patients within the hospitalization (40 +/- 10 days) (Mean +/- SD). In he overall series, liver function, evaluated by Child-Pugh classification, a higher blood-related requirements and cyclosporine levels were observed more in those who experienced renal failure than those who did not (p < 0.05). Early renal failure was related with preoperative (liver function) and intraoperative (blood requirements) factors and several causes (nephrotoxic drugs and graft failure) other than cyclosporine were present in patients who developed late renal impairment. No mortality. No mortality was associated with renal failure. We conclude that renal failure a) is a common finding after liver transplantation, b) the pathogenesis of this complication is multifactorial and, c) in not related with a poor outcome.