Recurrent hepatitis C treatment with direct acting antivirals - a real life study at a Brazilian liver transplant center.

Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2-228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2-16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied.

Case Reports and Literature Review About Family Autonomy in the Process of Donation of Organs and Gametes: An Ethical and Legal Analysis.

The recovery or collection of postmortem semen raises relevant ethical and social concerns. In this study we report 2 cases witnessed by the authors in an organ procurement organization in Brazil. The patients had a diagnosis of brain death, were organ donors, and had no consent for the use of postmortem sperm. In Brazil, the diagnosis of brain death has been clearly established since 1997, with the most recent update in 2017, but has not considered the possibility of the collection of sperm or eggs from the donor. A review of the world literature has been carried out, as well as current legislation in different countries, including Brazil, with special interest in the impact on the autonomy of the deceased (informed consent or not), the wife, the generation of the child and their rights, and the ethical role of the physician.

Recurrent hepatitis C treatment with direct acting antivirals - a real life study at a Brazilian liver transplant center

Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2-228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2-16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied.

Mortality Predictors After Liver Transplant in the Intensive Care Unit.

BACKGROUND: The goal of this study was to evaluate the predictive factors of mortality in patients after liver transplantation in an intensive care unit from the University Hospital. METHODS: This observational study was conducted by using a database analysis of University Hospital. The sample consisted of patients after liver transplantation registered in the database. The study variables of Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Disease Classification II (APACHE II), Model for End-Stage Liver Disease, and Child-Pugh scores, and the days of hospitalization in intensive care unit, mechanical ventilation time, and reintubation rate, were correlated. Statistical analysis was performed by using the χ2 test or Fisher exact test, the Mann-Whitney test, and logistic regression analysis. RESULTS: Fifty-eight individuals were analyzed. In the death group, the days of hospitalization in the intensive care unit were within 12 ± 14 days, the time of mechanical ventilation was 180 ± 148 hours, the APACHE II value was 17.6 ± 7.3, the Sequential Organ Failure Assessment score was 8.2 ± 2.7, and reintubation was 40%. In the multivariate regression, the predictive indexes of mortality were the mortality given by APACHE II (odds ratio, 1.1; CI, 1.03-1.17; P = .004), mechanical ventilation time (odds ratio, 1.02; CI, 1.01-1.04; P = .001), and reintubation (odds ratio, 9.06; CI, 1.83-44.9; P = .007). An increase of 1 unit in APACHE II mortality increases the risk of death by 10.2%, and each hour of mechanical ventilation increases the risk of death by 2.6%. CONCLUSIONS: The time of mechanical ventilation, orotracheal reintubation, and the mortality given by APACHE II were the variables that best predicted death in this study.

Model for End-Stage Liver Disease Score Before Hepatic Transplantation and Root Mean Square of the Diaphragmatic Domes Affect Postoperative Extubation Time.

INTRODUCTION: The liver transplantation procedure, in addition to its prolonged surgical time, also predisposes to complications such as changes in respiratory mechanics, lung volumes, and gas exchange. OBJECTIVE: This study aims to verify if clinical factors related to the recipient, namely immediate pretransplant Model for End-Stage Liver Disease (MELD) score, surgical time, and root square metric (RMS) of the diaphragmatic domes, affect the extubation time after liver transplantation. METHOD: A prospective study, with a sample collected for convenience, gathered age (years), sex (male or female), MELD score immediately prior to transplantation (without the addition of special situation scores), and surgical time and time for extubation (in minutes). The latter were obtained from the physiotherapy team records, and surface electromyography was performed within 30 minutes after elective extubation, by a single researcher, with supplemental oxygen support, maintaining SpO2 ≥ 95% and following protocol of positioning and acquisition of electromyographic signals based on the study of Oliveira et al (2012). RESULTS: For the 21 patients studied, the RMS of the left dome showed a moderate-intensity correlation (-0.56) with the time of extubation, and linear multiple regression model the left dome (P = .013) and preoperative MELD score (P = .048) showed significant correlation with extubation time. CONCLUSION: The preoperative MELD score and the RMS values of the left dome significantly correlate with the time for patient extubation after liver transplantation, showing the effect of previously acquired muscle weakness and preoperative MELD score on postoperative outcome.

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.

Ischemia With Preconditioning in Wistar Rats Maintains Mitochondrial Respiration, Even With Mild Hepatocellular Disturbance.

INTRODUCTION: In hepatectomy or liver transplantation, preconditioning is a procedure indicated to protect the organ from ischemia-reperfusion injury (I-R). OBJECTIVE: Evaluate the effect of preconditioning after hepatic I-R in Wistar rats, through mitochondrial respiration, liver histology, and profile. METHOD: Twenty male Wistar rats, weighing on average 307.1 g, were anesthetized with sodium thiopental (25 mg/kg) intravenously and xylazine hydrochloride (30 mg/kg) intramuscularly. The animals were divided into 2 groups: the preconditioning group (PCG), which contained 10 animals, and the hepatic pedicle was isolated and submitted to clamping with microvascular clamp (10 minutes of ischemia and 10 minutes of reperfusion, followed by 30 minutes of ischemia and 30 minutes of reperfusion); and the simulated operation group (SOG), which contained 10 animals submitted to manipulation of the hepatic pedicle and observation for the same length of time, with blood collected for transaminase dosage measurements, and liver biopsy for evaluation of mitochondrial respiration and histologic liver analysis and after sacrificed under anesthesia. The project was approved by the Ethics Committee on Animal Experimentation CEEA/UNICAMP under protocol number 3905-1. RESULT: The PCG mitochondria showed the same respiration level as the SOG, when stimulated with the addition of adenosine diphosphate or carbonyl cyanide p-trifluoromethoxyphenylhydrazone. In the respiratory control ratio and resting of velocity of respiration the groups behaved in a similar way. The PCG presented high aspartate and alanine transaminases (P < .03) and about 60% of sinusoidal congestion and venous congestion in the histologic analysis when compared with SOG. CONCLUSION: We found that ischemia with preconditioning in Wistar rats can lead to mild histologic and biochemical dysfunction without leading to impairment of mitochondrial respiration.

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.

Clinical impact of culture-positive preservation fluid on solid organ transplantation: A systematic review and meta-analysis.

Contamination of the preservation fluid (PF) used for donated organs is a potential source of post-transplant infection. However, the information on this issue is scarce. We therefore conducted a systematic review and meta-analysis to assess the incidence of culture-positive PF and its impact on solid organ transplant (SOT) recipients. Seventeen studies were identified and included. The overall incidence of culture-positive PF was 37% (95% CI: 27% to 49%), and the incidence of PF-related infections among SOT recipients with PF cultures that grew pathogenic microorganisms was 10% (95% CI: 7% to 15%). There were differences in the rates of infections due to pathogenic microorganisms between SOT recipients who received pre-emptive treatment and those who did not, but without statistical significance. The mortality rate among SOT recipients with PF-related infection was 35% (95% CI: 21% to 53%). In conclusion, although contamination of the PF of donated organs is frequent, the incidence of PF-related infection is relatively low. A closely clinical and microbiologic monitoring of the SOT recipient in case of culture-positive PF, regardless of the type of microorganism isolated might be do in order to establish a prompt diagnosis of PF-related infection.

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.

Lung Ultrasound and Pulmonary Function Test in Cirrhotic Patients.

Lung ultrasound (LU) is useful in the diagnosis of pulmonary interstitial-alveolar syndrome (IAS) when B-lines are detected. Its prevalence and effect in lung function is not well studied in cirrhotic patients. The objective of this study was to detect the prevalence of interstitial-alveolar involvement with LU and correlate with pulmonary function test to distinguish the effect of ascites and B-lines in pulmonary function. This was an observational single-center study with 49 patients listed for liver transplantation submitted for LU and pulmonary function tests. Patients were divided into 4 groups: no ascites and no B-lines (n = 19), B-lines only (n = 19), ascites only (n = 6), and ascites and B-lines (n = 5). There was a worse forced vital capacity (FVC) in patients with B-lines only (76.1% ± 9.2; P = .0058) and ascites only (66.8% ± 10.2; P = .0010). 1-second forced expiratory volume (FEV1) also was lower in patients with B-lines only (78.5% ± 10.3; P = .0001), ascites only (71.3% ± 13.2; P = .0004), and B-lines and ascites (74.2% ± 7.6; P = .0035). Model for End-Stage Liver Disease score was worse in the group with ascites and B-lines (22.4 ± 10.1; P = .0229). B-Lines reduced FVC and FEV1 in our study and may be an independent factor in worsening pulmonary function in these patients.

Diaphragm Muscle Surface Electromyography in Patients Submitted to Liver Transplant and Eligible for Extubation.

INTRODUCTION: Liver disease induces many organic and metabolic changes, leading to malnutrition and weight and muscular function loss. Surface electromyography is an easily applicable, noninvasive study, through which the magnitudes of the peaks on the charts depict voluntary muscle activity. AIM: To evaluate the diaphragmatic surface electromyography of postoperative liver transplantation subjects. METHODS: Subjects were patients who underwent liver transplantation and extubation in the Clinical Hospital of State University of Campinas. Electromyography data were collected with support pressure of ≤10 cm H2O, Glasgow Coma Scale = 11, and minimum dosages of vasoactive drugs, and data were collected again 30 minutes after extubation. Signal collection was performed with sEMG System Brazil SAS1000V3 electromyograph and electrode stickers. Statistical analysis was performed using R software. RESULTS: The average time of surgery was 345.36 ± 125.62 minutes. Time from spontaneous mode until extubation was 417.14 ± 362.97 minutes. The RMS (root mean square) values of the right and left domes in spontaneous mode with minimal ventilation parameters were 26.68 ± 10.92 and 26.55 ± 10.53, respectively, and the RMS values after extubation were 31.93 ± 18.69 to 34.62 ± 13.55, for right and left domes. The last calculated pretransplant Model for End-stage Liver Disease score averaged 19.64 ± 8.41. CONCLUSION: There were significant differences between the RMS of the diaphragm domes under mechanical ventilation and after extubation, showing lower effectiveness of the diaphragm muscle against resistance, without the aid of positive pressure and the existing overload of the left dome.

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.

Immunoexpression of Heat Shock Protein 70, Glypican 3, Glutamine Synthetase, and Beta-Catenin in Hepatocellular Carcinoma After Liver Transplantation: Association Between Positive Glypican 3 and Beta-Catenin With the Presence of Larger Nodules.

BACKGROUND: Hepatocellular carcinoma (HCC) is the 6th leading cause of cancer worldwide. Its recurrence ranges from 6% to 26%. In the literature, many factors are associated with higher risk of recurrence, without a clear definition of the best method that could predict this highly lethal event. OBJECTIVE: The aim of this study was to evaluate the immunoexpression of immunohistochemical markers: HSP70, glypican 3, glutamine synthetase, and beta-catenin, as well as studying their association with tumor characteristics and prognosis of patients undergoing liver transplantation for HCC. METHODS: We studied 90 patients who underwent liver transplantation from 1998 to 2012. Afterwards we evaluated factors related to survival, tumor recurrence, and the correlation of expression of the immunohistochemical markers. RESULTS: Immunohistochemical marker glutamine synthetase showed a positive trend toward better survival. HSP70-positive patients had a higher prevalence of histologic grade III. Patients with positive glypican 3 showed larger lesions and a higher number with AFP >200 ng/mL. Patients with positive beta-catenin showed larger nodules and more with histologic grade III. The association between beta-catenin and glypican 3 showed positive association with larger nodules. CONCLUSIONS: Most of the markers studied had a correlation with at least one of the variables studied, confirming our hypothesis that these markers can indeed assist in assessing the prognosis of patients undergoing liver transplantation for HCC.

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.

Later Evaluation of Ischemia and Reperfusion by the Pringle Maneuver in Wistar Rats, Demonstrating That Hepatic Lesions Can Be Reversible.

OBJECTIVE: There has been much research on hepatic ischemia and reperfusion by means of short or longer interruption of the portal triad. The aim of this work was to evaluate the mitochondrial respiratory activity and liver histology at 2 different times after the Pringle maneuver. METHODS: Twenty-eight male Wistar rats, weighing ∼308 g, with histologic and mitochondrial study: immediate ischemic group (IIG; 40 minutes; 9 animals) and late ischemic group (LIG; 28 days; 9 animals). The rats were anesthetized and underwent a U-incision in the abdomen. In a simulated operation, manipulation of the hepatic pedicle was performed (5 animals immediate [ISG] and 5 late [LSG]). The hepatic pedicle was clamped for 20 minutes of ischemia foloowed by 20 minutes of reperfusion. The animals were killed under anesthesia. RESULTS: Mitochondria when stimulated by adenosine diphosphate or carbonylcyanide p-trifluoromethoxyphenylhydrazone had a significant respiratory reduction (P < .001). The respiratory control ratio in the LIG was altered (P < .02) compared with IIG. In the resting state, there was no change in the velocity of respiration between ischemic groups. Histopathologic findings showed 55.5% sinusoidal dilatation in IIG and 66.6% in LIG; 77.7% ballooning in IIG and 55.5% in LIG; and 11.1% focal necrosis in both IIG and LIG. CONCLUSIONS: The oxidative phosphorylation system recovered with improvement in mitochondrial respiration; however, morphologic recovery was associated with the type and intensity of injury.

Survival benefits of interferon-based therapy in patients with recurrent hepatitis C after orthotopic liver transplantation.

Recurrent hepatitis C after orthotopic liver transplantation (OLT) is universal and can lead to graft failure and, consequently, reduced survival. Hepatitis C treatment can be used to prevent these detrimental outcomes. The aim of this study was to describe rates of hepatitis C recurrence and sustained virological response (SVR) to interferon-based treatment after OLT and its relationship to survival and progression of liver disease through retrospective analysis of medical records of 127 patients who underwent OLT due to cirrhosis or hepatocellular carcinoma secondary to chronic hepatitis C between January 2002 and December 2013. Fifty-six patients were diagnosed with recurrent disease, 42 started interferon-based therapy and 37 completed treatment. Demographic, treatment- and outcome-related variables were compared between SVR and non-responders (non-SVR). There was an overall 54.1% SVR rate with interferon-based therapies. SVR was associated with longer follow-up after treatment (median 66.5 vs 37 months for non-SVR, P=0.03) and after OLT (median 105 vs 72 months, P=0.074), and lower rates of disease progression (15 vs 64.7%, P=0.0028) and death (5 vs 35.3%, P=0.033). Regardless of the result of therapy (SVR or non-SVR), there was a significant difference between treated and untreated patients regarding the occurrence of death (P<0.001) and months of survival (P<0.001). Even with suboptimal interferon-based therapies (compared to the new direct-acting antivirals) there is a 54.1% SVR rate to treatment. SVR is associated with improved survival and reduced risks of clinical decompensation, loss of the liver graft and death.