Clinical Profile of Patients With Diabetes Mellitus and Liver Transplantation: Results After a Multidisciplinary Team Intervention.

BACKGROUND: Over the years, survival after liver transplantation has increased and metabolic complications are becoming more common, contributing to patients' morbidity and mortality. The objectives of this study were to describe a population of patients with hepatic transplantation and diabetes mellitus (DM), evaluate the frequency of metabolic complications, and assess the impact of a multidisciplinary team on DM management. MATERIALS AND METHODS: This was a retrospective study involving interview and medical record analysis of 46 consecutive patients followed at the diabetes mellitus and liver transplantation unit of a tertiary university hospital, all evaluated by a multidisciplinary team. RESULTS: Of all patients, 76.1% were men, with a median age 60 years old (interquartile range: 56 to 65 years) and liver transplantation time of 5 years (interquartile range: 0.6-9 years). Hypertension, hypercholesterolemia, hypertriglyceridemia, alcoholism, and smoking were present in 47.8%, 34.8%, 23.9%, 34.8%, and 30.4% of the patients, respectively. The most frequent immunosuppressant in use was tacrolimus (71.1%). Regarding nutritional status, 37.9% of patients were classified as overweight according to body mass index, and 41.2% were considered overweight according to the triceps skin fold. The median glycosylated hemoglobin and weight before and after intervention of the multidisciplinary team in all 46 patients were, respectively, 7.6% (5.7% to 8.8%) versus 6.5% (5.7% to 7.7%); P = .022 and 70.5 kg (64.7 to 82.0 kg) versus 71.6 kg (65.0 to 85.0 kg); P = .18. CONCLUSIONS: Hypertension and dyslipidemia were common in transplanted patients with DM. Intervention of the multidisciplinary team resulted in a significant improvement in glycosylated hemoglobin without significant weight gain.

Frequency of Thyroid Dysfunction in Patients With Diabetes Mellitus Before and After Liver Transplantation.

BACKGROUND: There is mutual influence between the liver and thyroid hormone metabolism. Patients with diabetes mellitus (DM) also have an increased prevalence of thyroid disorders (TDs). The objectives of this study were to evaluate the frequency of TD before and after liver transplantation (LT) in a population of patients with DM as a whole and when categorized by sex. MATERIALS AND METHODS: This was a retrospective study involving interview and medical record analysis of 46 consecutive patients followed at the diabetes mellitus and liver transplantation unit of a tertiary university hospital. RESULTS: Of all patients, 76.1% were men with a median age of 60 years old (interquartile range: 56 to 65 years) and time since LT of 5 years (range, 0.6 to 9 years). Hypertension, hypercholesterolemia, hypertriglyceridemia, alcoholism, and smoking were present in 47.8%, 34.8%, 23.9%, 34.8%, and 30.4% of the patients, respectively. The most frequent immunosuppressant in use was tacrolimus (71.1%). TD was present in 4.3% and 13% before and after LT, respectively (P = .058). In women and men, these frequencies were 9.1% and 18.2% (P = .563), and 2.9% and 11.8% (P = .045), respectively. CONCLUSIONS: Frequency of TD was high both before and after LT. After transplantation, prevalence of TD increased in men and differences between males and females almost disappeared. Further studies are needed to assess if screening for TD before and after LT in patients with DM might be beneficial, especially in men.

Acute Liver Failure-25 Years at a Single Center: Role of Liver Transplantation in the Survival of Adult Patients.

BACKGROUND: Acute liver failure (ALF) leads to high morbidity and mortality and is characterized by an accelerated deterioration of hepatic function in patients without prior liver disease. The survival rate is <15% without liver transplantation (LT). The aim of this study was to describe the population of patients with ALF in the Unit of Liver Transplantation of the University of Campinas, Brazil, from 1991 to 2017, comparing those submitted and not submitted to LT. METHODS: The patients were divided into 2 groups: 1, listed but not transplanted; and 2, transplanted. RESULTS: There were 73 patients with ALF listed for LT, with a mean age of 33.6 years, 49 (67.1%) female and 24 (32.9%) male. Group 1, with 32 patients, had a mean age of 29.3 years; 26 (81.25%) died on the waiting list; 6 (8.45%), with a mean age of 12.33 years, were removed from the list because of recovery of liver function. Considering only adult patients, the mortality without LT was 96.29%. Group 2 had 41 patients, with a mean age of 37.1 years, and a 30-day survival of 41.02%. Thus, LT led to a significant improvement in the survival of adult patients with ALF. The time of surgery, packed red blood cells, and intraoperative plasma, were associated with LT survival after logistic regression study, whereas age, body mass index, bilirubin, international normalized ratio, creatinine, sodium, and Model for End-Stage Liver Disease score were not. CONCLUSIONS: ALF affects an active age range, and LT decreases mortality; there was no good preoperative prognostic indicator to assess which patients would benefit from transplantation.

Acute Liver Failure Induced by Carthamus tinctorius Oil: Case Reports and Literature Review.

BACKGROUND: Acute liver failure (ALF) is a clinical syndrome that results from the abrupt loss of liver function in a patient without previous liver disease. The most frequent causes are viral hepatitis, drug induced, and autoimmune disease, but in 20% of cases no cause is identified. Carthamus tinctorius (safflower) oil is used as a dietary supplement for weight loss and antioxidant. There are 4 cases described in the literature of ALF induced by the use of this substance. The objective of this study was to report 3 cases of ALF treated at the Clinical Hospital of the State University of Campinas that suggest the use of C tinctorius oil as a probable etiologic factor. CASE REPORTS: The 3 patients had a diagnosis of ALF according to the King's College criteria. All had a history of ingestion of this oil for weight loss. During etiologic evaluation, viral hepatitis, autoimmune diseases, or any other drug cause were excluded, thus pointing to C tinctorius oil as the triggering factor. All 3 patients underwent liver transplantation: 2 had good postoperative evolution, and 1 died 12 days after the procedure. CONCLUSIONS: Two cases are described in which the hepatic insufficiency induced by C tinctorius oil was successfully treated through liver transplantation. This highlights the risk of misuse of this substance for weight loss.

Association Safety of Liver Preservation Solutions at the State University of Campinas From 2010 to 2014.

The probable reason for mixing solutions during the harvesting procedure is due to the presence of multiple transplant teams that have their own solution usage tradition. Despite numerous studies comparing the efficacy of different preservation solutions, there is no study addressing the associating solution and if there is any impact on liver graft and patient survival. The aim was to evaluate the effect of the association of preservation solutions during the harvesting procedure on liver transplantation outcomes, especially in relation to the degree of preservation injury in the postreperfusion period and patient survival. We analyzed 206 transplants that were distributed as follows: when there was association (89/206 = 43.2%) and when there was no association (117/206 = 56.8%). There was a statistically significant difference in relation to the degree of preservation injury correlated to cold ischemia time (P = .009, odds ratio 1.992; 95% confidence interval 1.185-3.347). Severe harvesting (grades III and IV) was 71.8% when the solution was not associated (P = .008). There was no difference regarding patient survival either. We found that the association of liver preservation solutions has no impact on patient survival, so it can be done safely. The best survival rate was associated with minimal harvesting.

Immunomodulation, Acute Renal Failure, and Complications of Basiliximab Use After Liver Transplantation: Analysis of 114 Patients and Literature Review.

Basiliximab is considered to be effective in preventing cellular rejection (CR) in solid organ transplantation and is commonly used for renal transplants. The aim of this study was describe the population of patients undergoing orthotopic liver transplantation (LT) receiving basiliximab in the period 2012-2016 in the liver transplant service at the State University of Campinas, São Paulo, Brazil. We analyzed 114 patients who underwent LT and received basiliximab; 83 (72.8%) were male and 31 (27.2%) female, with an overall mean age of 54.3 years. Immunosuppression was performed with corticosteroids during anesthetic induction, and postoperatively with tacrolimus in 85.5%, sodium mycophenolate in 81.7%, cyclosporine in 12.7%, and everolimus in 15.5% of patients. CR was observed in 25.43% of patients, confirmed by biopsy in 15 patients: 50% acute CR, 21.42% late acute CR, and 28.57% chronic CR. Thus, the data are consistent with the literature regarding the benefit of using basiliximab as induction therapy while reducing the incidence of CR after LT, but on univariate analysis to evaluate factors associated with the occurrence of CR, the analyzed variables did not present statistical significance. There was acute renal failure (ARF) in 46.84% of patients and hemodialysis was performed in 20% of cases. In a previous series in our service, there was an ARF rate of 50%, so the incidence reduction of ARF after basiliximab use was 3.16%. Moreover, there was 6.95% hepatic artery thrombosis, 2.6% portal vein thrombosis, 2.6% biliary fistulas, 17.4% pneumonia, and 3.4% sepsis, which did not differ from the literature or from our earlier study without the use of basiliximab, suggesting the safety of this medication. In conclusion, in this series, basiliximab influenced the decrease of the CR incidence with no proven benefit on improvement in the ARF.

Factors Related to Hepatocellular Carcinoma Recurrence After Liver Transplantation-A Brazilian Multicenter Study.

BACKGROUND: Liver transplantation (LT) is a curative treatment option for hepatocellular carcinoma (HCC); recurrent HCC after liver transplantation (HCC-R) is diagnosed in 9%-16%. The objective of this study was to evaluate which factors are associated with R-HCC after liver transplantation. METHODS: This retrospective real-life study analyzed 278 LTs from 3 reference centers (2,093 LTs) in Brazil from 1988 to 2015. HCC-R with histologic confirmation was seen in 40 patients (14.4%). RESULTS: Most of them were male with cirrhosis secondary to viral hepatitis. Only 37.5% underwent chemoembolization, and 50% had cold ischemia time >8 hours. From the explant analysis, most of the patients were outside Milan criteria and 37.5% had microvascular invasion. The donors were mostly male, and the median intensive care unit time was >3 days. The Kaplan-Meier survival was lower according to alpha-fetoprotein (AFP) >200 ng/dL (P = .02), and older donors and more blood transfusions were risk factors for HCC-R death. CONCLUSION: AFP >200 ng/mL was associated with lower survival, and older donors and more blood transfusions were risk factors for death after HCC-R. A trend to lower survival was observed in patients who did not have chemoembolization and had cold ischemia times >8 hours.

Hepatic Artery Thrombosis After Liver Transplantation: Five-Year Experience at the State University of Campinas.

BACKGROUND: Hepatic artery thrombosis (HAT) is reported in 4%-15% of orthotopic liver transplants. Risk factors include technical error in the anastomosis, vascular anatomic variation, and high microvascular resistance. The aim of this study was to verify the incidence of HAT, early or late, and possible risk factors. METHODS: This was a retrospective study from January 2007 to December 2012 at the State University of Campinas. Variables analyzed were age, sex, cold and warm ischemia times, underlying disease, presence of hepatocellular carcinoma, Model for End-Stage Liver Disease (MELD) score, arterial anatomic variation in the graft, cytomegalovirus (CMV) infection, rejection, biliary complications, retransplantation rate, and survival. RESULTS: The incidence of HAT was 21/263, or 7.9%. Pure average MELD score was 22 ± 7.4. There was vascular anatomic variation in the graft in 14.2% of cases, in the majority (66.6%) a right hepatic artery from the superior mesenteric artery, and 4.76% of patients had CMV infection and acute cellular rejection (1 case each). There were biliary complications in 38% of patients, 13.3% of cases in patients with early HAT, and 100% of patients with late HAT (P = .002). Body mass index in late HAT was higher (P = .01). CONCLUSIONS: Late HAT was related to a significant increase in biliary complications (stenosis), and the survival rate was similar at 5 years.

Evaluation of Recurrence Predictors and Survival Probability After Liver Transplantation for Hepatocellular Carcinoma: Analysis From a Single Center.

BACKGROUND: Liver transplantation is the criterion standard treatment for hepatocellular carcinoma, but tumor recurrence remains a problem leading to a worse prognosis. We aimed to evaluate factors associated with recurrence of hepatocellular carcinoma and survival after this procedure. METHODS: We retrospectively reviewed data from 101 patients submitted to liver transplantation because of hepatocellular carcinoma from January 2005 to January 2012 at our single center. Univariate and multivariate analyses were performed to identify preoperative factors and histologic findings associated with lower survival rates and recurrence. The significance level was 5%. RESULTS: There was recurrence in 10 cases (9.9%), with an average time of 25.28 ± 26.92 months. Microvascular invasion (P = .005; hazard ratio [HR], 4.94; 95% confidence interval [CI], 1.42-17.12) was an independent factor for recurrence. Microvascular invasion (P = .035; HR, 1.87; 95% CI, 1.04-3.25) and tumors outside the criteria of the University of San Francisco (P = .046; HR, 1.81; 95% CI, 1.01-3.25) were independent factors for the risk of death. Poorly differentiated tumors had a higher level of alphafetoprotein (P = .03), and values <100 ng/mL were associated with well differentiated tumors. CONCLUSIONS: Microvascular invasion was associated with recurrence and lower survival. Tumors outside the criteria of the University of California, San Francisco had lower survival. Alpha-fetoprotein levels >100 ng/mL were associated with poorly differentiated tumors.

Variables associated with the risk of early death after liver transplantation at a liver transplant unit in a university hospital.

BACKGROUND: Graft dysfunction after liver transplantation is a serious complication that can lead to graft loss and patient death. This was a study to identify risk factors for early death (up to 30 days after transplantation). METHODS: It was an observational and retrospective analysis at the Liver Transplantation Unit, Hospital de Clinicas, State University of Campinas, Brazil. From July 1994 to December 2012, 302 patients were included (>18 years old, piggyback technique). Of these cases, 26% died within 30 days. For analysis, Student t tests and chi-square were used to analyze receptor-related (age, body mass index, serum sodium, graft dysfunction, Model for End-Stage Liver Disease score, renal function, and early graft dysfunction [EGD type 1, 2, or 3]), surgery (hot and cold ischemia, surgical time, and units of packed erythrocytes [pRBC]), and donor (age, hypotension, and brain death cause) factors. Risk factors were identified by means of logistic regression model adjusted by the Hosmer-Lemeshow test with significance set at P < .05. RESULTS: We found that hyponatremic recipients had a 6.26-fold higher risk for early death. There was a 9% reduced chance of death when the recipient serum sodium increased 1 unit. The chance of EGD3 to have early death was 18-fold higher than for EGD1 and there was a 13% increased risk for death for each unit of pRBC transfused. CONCLUSIONS: Donor total bilirubin, hyponatremia, massive transfusion, and EGD3 in the allocation graft should be observed for better results in the postoperative period.

Evaluation of functional status, pulmonary capacity, body composition, and quality of life of end-stage liver disease patients who are candidates for liver surgery.

INTRODUCTION: Muscular weakness in combination with malnutrition can induce a global motor impairment and physical inactivity, adversely impairing the daily living activities and quality of life of end-stage liver disease patients who are candidates for liver transplantation. OBJECTIVES: To evaluate functional status, pulmonary capacity, body composition and quality of life in end-stage liver disease patients who are candidates for liver transplantation; to verify if there is a correlation between the functional variables of the individuals tested through the 6-minute walk test (6MWT) and covariables: pulmonary function test (PFP), quality of life and body composition. METHODS: This study was carried out at the Liver Transplantation Unit of the State University of Campinas (UNICAMP). We included 46 patients with end-stage liver disease who underwent the following evaluations: medical history, quality of life questionnaire "Short Form 36" (SF-36), surface electromyography (sEMG) of the diaphragm and rectus abdominis muscles, body composition assessment by electrical vioimpedance (BIA), 6MWT and PFP. RESULTS: Univariate analysis and Pearson's correlation found correlations between distance walked on 6MWT and QOL (P = .006 and P = .02) and TBW (P = .5 and P = .02). Pearson's correlation were found between respiratory variables of 6MWT, QOL, and PFP. CONCLUSION: The functional status may be correlated to body composition, quality of life and pulmonary capacity of patients with liver disease, candidates for transplantation.

Neurological complications prevalence and long-term survival after liver transplantation.

INTRODUCTION: Neurological postsurgical complications are a significant cause of morbidity and mortality occur in transplant recipients impacting their survival. METHODS: We analyzed the medical records of 269 patients who underwent transplantation between 2000 and 2011, after application of the exclusion criteria Neurological complications were examined according to the period in which they appeared: immediate (1-30 day) early (31-180 days), and late (after 180 days). The survival analysis was based on the first complication. RESULTS: The majority of transplant recipients were males (73.2%) and white (97.1%) with an overall median age of 49 (range, 18-73) years. Regarding the etiology for transplantation, the most common causes were hepatitis C virus (56.5%) and alcohol (33.1%). Complications, appearing in 29.4% (immediate), 31.5% (early), and 39.1% (late) cases, were encephalopathy, confusion, tremors, headache, and stroke. Patients who had the first complication between 1 and 6 months showed greater mortality than those who had one after 6 months. CONCLUSIONS: Neurological complications led to longer hospital stays with greater early morbidity and mortality. Knowledge of these complications appears to be extremely important for the multidisciplinary transplantation team to decrease its prevalence as well as to diagnose and treat early.

Sirolimus as rescue therapy after liver transplantation.

UNLABELLED: Sirolimus has immunosuppressive properties and antitumor effects. It was prescribed in liver transplantation initially in association with calcineurin inhibitors because of its lower nephrotoxic and neurotoxic effects and its potential antitumor effects. The aim of this study was to analyze the use of sirolimus as rescue therapy for liver transplant patients. METHODS: We retrospectively analyzed all 15 patients treated with sirolimus from 2009 to 2011 among 150 liver transplantations. We analyzed pre- and postconversion data. With statistical analysis using the Student's t-test. RESULTS: Sirolimus was the immunosuppressant therapy in 15 of 150 (10%) patients. Their average age was 56.2 years (range, 42-69) including 9 men (60%). The mean time between liver transplantation and the introduction of sirolimus was 24.6 months (range, 1-120). Sirolimus remained as the sole medication for 4 patients (26.6%). The overall time of sirolimus thereby averaged 14.3 months (range, 1-18). The reasons for the introduction of sirolimus were acute rejection (n = 8; 53.3%), chronic rejection (n = 2; 13.3%), development of malignancy (n = 3; 20%) or prior hepatocellular carcinoma (n = 2; 13.3%). Among 9 patients who initiated sirolimus because of rejection, 7 (77.7%) showed improvement in serum liver enzymes. Among the 3 (33.3%) patients who displayed renal insufficiency before the introduction of sirolimus (creatinine level > 1.5 mg/dL) 1 showed improvement with a decrease of ≥50%. The average follow-up was 18 months (range, 1-36). The average sirolimus level during the first 3 months was 10.3 ng/mL (range, 6.1-19.3). All patients developed side effects such as anemia, hypertriglyceridemia, hypercholesterolemia, and infection. In conclusion, sirolimus was useful as rescue therapy.

Predicting survival after liver transplantation using up-to-seven criteria in patients with hepatocellular carcinoma.

BACKGROUND: Liver transplantation is a controversial issue in the initial management of hepatocellular carcinoma (HCC). The aim of this study was to demonstrate that up-to-seven could be useful as a model in evaluating potential candidates for liver transplantation for HCC. METHODS: Between January 1997 and December 2010, 84 patients undergoing liver transplantation were analyzed for HCC. Pathologic variables included the number of lesions, maximal tumor diameter, vascular invasion, and tumor grade. The following variables were recorded: Age, gender, recurrence of HCC, survival, donor age, incidental, Milan criteria, Model for End-Stage Liver Disease score, and alpha-fetoprotein (AFP) levels. To evaluate variables we used the Kaplan-Meier method, Cox regression and Kolmogorov-Smirnov test. RESULTS: There were 68 (80.9%) patients within up-to-seven criteria and 16 (19.1%) beyond this criteria. AFP levels were 96.4 versus 464.3 ng/dL in patients within versus beyond up-to-seven criteria. The median diameter of the largest nodule was 22.2 versus 32.0 mm in patients within versus beyond up-to-seven criteria, respectively. The median sum of nodules was 1.8 and 5.6 nodules in patients within versus beyond up-to-seven criteria. Vascular invasion was present in 11 (13.0%) patients within versus 7 (8.3%) beyond. Recurrence was observed in 9 (10.7%) patients and only 3 were beyond up-to-seven criteria, 2 had vascular invasion, and another showed poor differentiation. Post liver transplantation survival rates were 87.7%, 74.5%, and 65.3% at 1, 3, and 5 years in patients within up-to-seven versus 80.7%, 51.7%, and 32.1% beyond (P = .03). Similar results were observed when we applied Milan criteria or expanded Milan criteria. The largest nodule was the only predictive factor after proportional hazard Cox regression application (Beta = 0.037; exponent = 1.0377; Wald = 4.542; P = .03). In the present study, up-to-seven criteria could be useful to evaluate potential liver transplant candidates due to HCC.

Can pre-liver transplantation renal insufficiency using a creatinine clearance calculator predict long-term survival?

INTRODUCTION: Renal insufficiency can be associated with poor long-term survival of liver transplant recipients. OBJECTIVE: The objective of this study was to study renal insufficiency observed pretransplantation and its long-term impact after liver transplantation. METHODS: We analyzed retrospectively an electronic database collected prospectively including transplant records from June 1994 to October 2010 using piggyback venous reconstruction. The exclusion criteria were chronic kidney disease, acute hepatic failure, children up to 12 years of age, and retransplantations. Renal insufficiency was defined by the creatinine clearance (CCr) calculated using the Cockcroft-Gault method. Patients were distributed into 3 groups: CCr >90, between 90 and 60, and >60 mL/min/1.73 m(2). The survival rate was calculated using the Kaplan-Meier method and proportional hazards Cox regression analysis using death and CCr as stratifying variables evaluated predictive factors for survival. The groups were compared using the Kruskal-Wallis test with significant differences at P < .05. RESULTS: Among the 305 patients those who showed preoperative and postoperative CCR of >90 were 187/59.9% and 82/26.3%, 60 to 90 were 77/24.7% and 74/23.7%, or <60 mL/min/1.73 m(2) were (41/13.1% and 149 (47.7%). Patients with preoperative CCr <60 mL/min/1.73 m(2) showed worse short- and long-term survivals as well as the longest intensive care unit and hospital stays (P = .034). The only predictive donor factor was age older than 40 years namely, the greatest hemotransfusion needs and postoperative liver and renal dysfunction (Chi square = 100.6064; P = .00001). The area under the curve (AUC) obtained using an receiver operating characteristic (ROC) analysis was 0.563 (95% CI 0.498-0.627) with a cut off of 30.25. CONCLUSION: Pre-liver transplantation renal insufficiency seemed to be a predictive factor for long-term survival.