Sérgio Mies

Risk Factors for Development of Acute Renal Failure After Liver Transplantation

Background. Acute renal failure (ARF) is a common complication after liver transplantation (LTx). Identification of risk factors may prevent the development and attenuate the impact of ARF on patients outcome after LTX. Methods. Retrospective analysis of variables in the pre, intra, and postoperative periods of 92 patients submitted to LTx was performed in order to identify risk factors for development of ARF after LTx. ARF was defined as serum creatinine ≥2.0 mg/dL in the first 30 days after LTx. Univariate and multivariate analysis by logistic regression were performed. Results. ARF group comprised 56 patients (61%). Preoperative serum creatinine was higher in ARF group. During the intraoperative period, ARF group required more blood transfusions, developed more episodes of hypotension and presented longer anesthesia time. In the postoperative period, ARF group presented higher serum bilirubin and more episodes of hypotension. Dialysis was required in 10 patients (11%). The identified risk factors for development of ARF were: preoperative serum creatinine >1.0 mg/dL, more than five blood transfusions in the intraoperative period, hypotension during intra and postoperative periods. The identified mortality risk factors were hypotension in the postoperative period and no recovery of renal function after 30 days. Conclusions. Several factors are involved in the pathogenesis of ARF after LTx and may influence patients outcome and mortality. Pretransplant renal function and hemodynamic conditions in the operative and postoperative periods were identified as risk factors for development of ARF after LTx. Nonrenal function recovery and postoperative hypotension were identified as mortality risk factors after LTx.

Bacterial translocation during liver transplantation: A randomized trial comparing conventional with venovenous bypass vs. piggyback methods

The aim of this study was to evaluate the bacterial translocation in liver transplantation (LT), comparing the conventional and the piggyback methods. A total of 32 patients were randomized into the 2 groups. Samples of blood were collected from the radial artery, portal vein (PV) and hepatic vein (HV), in up to 120 minutes postreperfusion. The samples were sent for endotoxin level, as well as samples up to 2 minutes post‐perfusion were sent to culture. Hepatic artery and PV blood flows were measured at postreperfusion collection times. The results analyzed were: endotoxin concentration, its quantity, and hepatic clearance. The statistical treatment consisted of analyzing each groups mean profile. The analysis for endotoxin concentration in the radial artery was the deviation related to presurgery measure, and in the PV the deviation related to preclamping (PC) measure. The overall mean level of endotoxin concentration was 0.99 EU/mL in the artery, 1.30 EU/mL in the PV, and 1.22 EU/mL in the HV. The deviation was significant in the portal (P = 0.0031), but not in the artery samples (P = 0.2092). We detected a significant quantity of endotoxin in the artery and in the portal and the HVs (P < 0.001). There was no difference between the 2 groups and no hepatic clearance of endotoxin was detected either (P = 0.1515). All the cultures were negative. In conclusion, the study detected a significant translocation of endotoxin, but not of bacteria. The study also detected the absence of endotoxin hepatic clearance in both the piggyback and the conventional methods without any difference between them. Liver Transpl 13:488–496, 2007.

Randomized trial comparing pulmonary alterations after conventional with venovenous bypass versus piggyback liver transplantation

During the anhepatic phase of conventional liver transplantation (LT), the inferior vena cava (IVC) is cross‐clamped and venovenous bypass (VVB) is usually indicated for diversion of IVC and portal blood flow. VVB can theoretically lead to pulmonary complications due to the contact of the blood with the surfaces of the circuit. In the piggyback method, preservation of the IVC avoids VVB. The aim of this study is to compare pulmonary alterations after conventional with VVB versus piggyback LT. Sixty‐seven patients were randomized for conventional VVB (n = 34) or piggyback (n = 33) LT. Pulmonary static compliance (Cst) and PaO2/FIO2 ratio were measured pre‐ and post‐LT. Chest X‐rays were obtained daily from the 1st to the 5th postoperative day. Pre‐ and post‐LT Cst were 73.4 ± 36.0 mL/cm H2O and 59.7 ± 22.0 mL/cm H2O in the conventional group and 69.1 ± 20.0 mL/cm H2O and 58.7 ± 27.1 mL/cmH2O in the piggyback group. The difference between the two groups was not significant (P = .702). Cst significantly decreased after LT (P = .008). The pre‐ and post‐LT PaO2/FIO2 were 455.6 ± 126.6 mm Hg and 463.1 ± 105.9 mm Hg in the conventional group and 468.9 ± 114.1 mm Hg and 483.3 ± 119.8 mm Hg in the piggyback group. The difference among the two groups was not significant (P = 0.331). There was no significant difference after LT (P = .382). Upon the radiological evaluation, piggyback group presented a higher frequency of pulmonary infiltrates (80.6% vs. 50.0%; P = .025). In conclusion, piggyback LT recipients have a higher rate of pulmonary infiltrates when compared to those operated upon using the conventional VVB method. (Liver Transpl 2004;10:425–433.)

Familial amyloidotic polyneuropathy type 1 in Brazil is associated with the transthyretin Val30Met variant

UNLABELLED Familial amyloidotic polyneuropathy type 1 (FAP1) is an inherited systemic amyloidosis that is secondary to the deposition of transthyretin (TTR) variants in peripheral nerves and in certain visceral organs. More than 50 distinct mutations have already been described in the TTR gene. Yet, the most common mutation found worldwide is a substitution of valine for methionine in position 30 (Val30Met). Currently, the variants of TTR in Brazilian FAP1 patients remain largely unknown and the aim of this study was to analyze the frequency of the TTR Val30Met mutation in such Brazilian subjects. METHODS Thirty-two FAP1 patients belonging to 24 different families were studied for the presence of Val30Met variant by PCR-RFLP. RESULTS All Brazilian FAP1 subjects studied were positive for the TTR Val30Met variant. As expected, all of them were heterozygous for the mutation. CONCLUSION TTR Val30Met mutation was the sole TTR variant found in Brazilian FAP1 patients in this cohort, and it was present even in those subjects without a clear history of Portuguese ancestry.

No evidence of de novo amyloidosis in recipients of domino liver transplantation: 12 to 40 (mean 24) month follow-up.

UNLABELLED Domino liver transplantation (DLT) has been performed for selected recipients at several centers, but de novo amyloidosis in recipients of livers from patients with familial amyloid polyneuropathy (FAP) remains a serious concern. AIM To evaluate the occurrence of de novo amyloidosis in recipients of DLT. PATIENTS AND METHODS Seven recipients of FAP livers were followed for clinical and electroneuromyographic signs of FAP and also for de novo amyloid deposition in the gut. RESULTS No signs and symptoms of de novo FAP nor any evidence of amyloid deposits in the gut were observed in recipients of DLT after a mean follow-up of 24 [12-40] months. CONCLUSIONS Signs and symptoms of FAP do not occur early in recipients of DLT. These livers could therefore be offered to patients suitable for conventional LT, particularly older subjects in whom the event of de novo amyloidosis would seem improbable.

Systemic and Hepatic Hemodynamics in Hepatosplenic Manson's Schistosomiasis with and Without Propranolol

Systemic and hepatic hemodynamics wereprospectively studied in 11 patients with Mansonsschistosomiasis and portal hypertension, as well asalterations resulting from the use of propranolol. Itwas decided that patients whose portal pressure was reducedby 30% with the use of the drug would not undergosurgery and that treatment would consist of the chronicuse of propranolol, associated with sclerosis of esophageal varices. This objective was not metby any of the patients whose portal pressure wasmeasured and the study was interrupted. Results showthat patients with Mansons schistosomiasis and portal hypertension have hyperdynamic circulation,mild pulmonary hypertension, greatly increased splenicblood flow, and preservation of total hepatic bloodflow. Administration of propranolol correctshyperdynamic circulation, aggravates pulmonary hypertension,does not alter portal pressure and reduces the sectorialportal blood flows, especially of the azygos vein, withmaintenance of total hepatic blood flow. These data favor the hypothesis of portaloverflow in the physiopathology of portal hypertensionof schistosomiasis.

Phenotypic expression of familial amyloid polyneuropathy in Brazil

Familial amyloid polyneuropathy (FAP) is an inherited amyloidosis mainly associated with transthyretin Val30Met variant. Clinical heterogeneity has been reported in different populations with FAP and Va130Met variant. In order to characterize FAP expression in Brazilians and to compare its features to those reported in other cohorts, 44 Brazilian patients (27 females, median age 36 [23–53] years) with FAP and the Val30Met variant were investigated. Approximately 40% of their family members, with the exception, of parents and siblings, had FAP. Most of the patients had symptoms of peripheral neuropathy at onset. Median age at onset was 32 [20–44] years. Earlier onset was observed in males (27 [20–43] years in males vs. 33 [20–44] years in females, P = 0.02) and in patients whose parents had FAP (31 [20–44] years vs. 40 [37–43] years in patients, respectively with and without affected parents, P = 0.03). Phenotypic expression of FAP in Brazil is similar to the one reported in Portugal, characterized by high disease penetrance, early onset, particularly in males and in subjects with affected parents, and major symptoms of peripheral neuropathy. These data highlight the influence of common genetic factors, shared by both groups of patients, in disease expression.

Human polyclonal anti-hepatitis B surface antigen immunoglobulin reduces the frequency of acute rejection after liver transplantation for chronic hepatitis B

BACKGROUND Use of polyclonal anti-hepatitis B surface antigen immunoglobulin (HBIg) has been shown to reduce hepatitis B virus (HBV) recurrence after liver transplantation (LT) and to decrease the frequency of acute cellular rejection (ACR). However, the protective role of HBIg against ACR remains controversial, since HBV infection has been also associated with a lower incidence of ACR. AIM To assess the relationship between HBIg immunoprophylaxis and the incidence of rejection after LT. METHODS 260 patients (158 males, 43 +/- 14 years old) submitted to LT were retrospectively evaluated and divided into three groups, according to the presence of HBsAg and the use of HBIg. Group I was comprised of HBsAg-positive patients (n = 12) that received HBIg for more than 6 months. Group II was comprised of HBsAg-positive patients that historically have not received HBIg or have been treated irregularly for less than 3 months (n = 10). Group III was composed of 238 HBsAg-negative subjects that have not received HBIg. RESULTS HBIg-treated patients (group I) had significantly less ACR episodes, when compared to group II and III. No differences between groups II and III were observed. CONCLUSIONS Long-term HBIg administration contributes independently to reduce the number of ACR episodes after LT.

Specific liver autoreactivity in schistosomiasis mansoni.

To investigate the possible involvement of autoimmune mechanisms in the development of hepatosplenic schistosomiasis (HSS), 234 patients with chronic Schistosoma mansoni infections were screened for a wide range of non-organ-specific autoantibodies as well as for antibodies reacting with the GOR peptide and with a liver-specific autoantigen, the hepatic asialoglycoprotein receptor (ASGP-R). Thirty-five (15.0%) were seropositive for antinuclear, smooth muscle or gastric parietal cell antibodies at low titres (≤1:80), and 15/176 (8.5%) had anti-GOR, all of whom had concomitant hepatitis C viral (HCV) infections. Anti-ASGP-R was found in 64 (27.4%) of the 234 patients at titres similar to those found in 18 untreated autoimmune hepatitis patients studied concurrently. Anti-ASGP-R seropositivity occurred significantly (P<0.005) more frequently in patients with HSS (62/190, 32.6%) than in those with hepatointestinal schistosomiasis (2/44, 4.5%), but did not correlate with severity of liver disease or with the presence of the non-organ-specific autoantibodies. Anti-ASGP-R was found significantly (P<<0.0005) less frequently in HSS patients who had had a splenectomy for portal hypertension (5/86, 5.8%) than in those who had not had a splenectomy (57/104, 54.8%). The findings suggest that liver-specific autoreactivity may play a role in the development of HSS.

Evaluation of predictive weaning indices for mechanical ventilation in liver transplantation

PATIENTS who have chronic liver disease, when in a terminal phase, often present ascitis, pleural effusion, and malnutrition. After liver transplantation these complications are associated with prolonged anesthesia, injury of the right diaphragm, infusion of blood-derived products, and surgical trauma, which result in alterations of gas exchange, reduction of pulmonary volume, and weakness of the respiratory muscles. This means that some parameters are required to ensure the successful weaning from mechanical ventilation immediately postoperative. Several indeces have been developed to predict successful weaning from mechanical ventilation. The indeces most often used are the spontaneous respiratory rate to tidal volume ratio (f/VT), 10 maximum inspiratory pressure (PImax), 11 and the partial arterial oxygen pressure to oxygen fraction inspired ratio (PaO2/FIO2). 12 In addition to these, our service has used maximum expiratory pressure (PEmax) measurements. These indeces are used for patients with chronic obstructive lung disease and healthy individuals. Unfortunately, no studies have been conducted to evaluate the efficacy of the method to wean patients from mechanical ventilation after liver transplantation. This study evaluates the efficacy of the f/VT, PaO2/FIO2, PImax and PEmax indeces as predictors for weaning from mechanical ventilation in liver transplantation patients.