Luiz Augusto Carneiro D’Albuquerque

Terlipressin versus Norepinephrine in the Treatment of Hepatorenal Syndrome: A Systematic Review and Meta-Analysis

Background Hepatorenal syndrome (HRS) is a severe and progressive functional renal failure occurring in patients with cirrhosis and ascites. Terlipressin is recognized as an effective treatment of HRS, but it is expensive and not widely available. Norepinephrine could be an effective alternative. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of norepinephrine compared to terlipressin in the management of HRS. Methods We searched the Medline, Embase, Scopus, CENTRAL, Lilacs and Scielo databases for randomized trials of norepinephrine and terlipressin in the treatment of HRS up to January 2014. Two reviewers collected data and assessed the outcomes and risk of bias. The primary outcome was the reversal of HRS. Secondary outcomes were mortality, recurrence of HRS and adverse events. Results Four studies comprising 154 patients were included. All trials were considered to be at overall high risk of bias. There was no difference in the reversal of HRS (RR = 0.97, 95% CI = 0.76 to 1.23), mortality at 30 days (RR = 0.89, 95% CI = 0.68 to 1.17) and recurrence of HRS (RR = 0.72; 95% CI = 0.36 to 1.45) between norepinephrine and terlipressin. Adverse events were less common with norepinephrine (RR = 0.36, 95% CI = 0.15 to 0.83). Conclusions Norepinephrine seems to be an attractive alternative to terlipressin in the treatment of HRS and is associated with less adverse events. However, these findings are based on data extracted from only four small studies.

Liver transplantation: fifty years of experience.

Since 1963, when the first human liver transplantation (LT) was performed by Thomas Starzl, the world has witnessed 50 years of development in surgical techniques, immunosuppression, organ allocation, donor selection, and the indications and contraindications for LT. This has led to the mainstream, well-established procedure that has saved innumerable lives worldwide. Today, there are hundreds of liver transplant centres in over 80 countries. This review aims to describe the main aspects of LT regarding the progressive changes that have occurred over the years. We herein review historical aspects since the first experimental studies and the first attempts at human transplantation. We also provide an overview of immunosuppressive agents and their potential side effects, the evolution of the indications and contraindications of LT, the evolution of survival according to different time periods, and the evolution of methods of organ allocation.

The Incapacity of the Surgeon to Identify NASH in Bariatric Surgery Makes Biopsy Mandatory

BackgroundNonalcoholic steatohepatitis (NASH) is a morbid condition highly related to obesity. It is unclear if the macroscopic liver appearance correlates with the histopathologic findings. The goal of this prospective study was to determine the relationship between the intraoperative liver appearance and the histopathologic diagnosis of NASH in morbidly obese subjects undergoing bariatric surgery. We also aimed to determine variables that could predict NASH preoperatively.MethodsConsecutive 51 subjects undergoing bariatric surgery without evidence of other liver disease underwent intraoperative liver biopsy. An intraoperative liver visual (macroscopic and tactile examination) was recorded. The liver aspect was compared with the liver histologic findings. Histological assessment was categorized into two groups: NASH and non-NASH (including normal histology and simple steatosis). Clinical and biochemical parameters were obtained from the patient databases and were compared between groups to identify preoperatively predictive factors of NASH.ResultsFrom 51 patients, only one presented totally normal histology. Forty-three (86.2%) presented simple steatosis, and seven (13.7%) were classified as NASH. Clinical parameters were not different between groups. At biochemical analysis, only VLDL cholesterol level was significantly higher in the NASH group (p = 0.037) but yet within the normal range. Association between macroscopic liver appearance and the presence of histological NASH is poor (sensitivity of 14%, specificity of 56%, positive predictive value of 5%, and negative predictive value of 80%).ConclusionsNo predictor of NASH was found. Surgeons’ evaluation could not identify NASH individuals. Routine liver biopsy during bariatric operations is mandatory to differentiate NASH and nonalcoholic fatty liver disease.

Liver transplantation in Latin America: The state-of-the-art and future trends

We reviewed the current status of liver transplantation in Latin America. We used data from the Latin American and Caribbean Transplant Society and national organizations and societies, as well as information obtained from local transplant leaders. Latin America has a population of 589 million (8.5% of world population) and more than 2,500 liver transplantations are performed yearly (17% of world activity), resulting in 4.4 liver transplants per million people (pmp) per year. The number of liver transplantations grows at 6% per year in the region, particularly in Brazil. The top liver transplant rates were found in Argentina (10.4 pmp), Brazil (8.4 pmp), and Uruguay (5.5 pmp). The state of liver transplantation in some countries rivals those in developed countries. Model for End-Stage Liver Disease-based allocation, split, domino, and living-donor adult and pediatric transplantations are now routinely performed with outcomes comparable to those in advanced economies. In contrast, liver transplantation is not performed in 35% of Latin American countries and lags adequate resources in many others. The lack of adequate financial coverage, education, and organization is still the main limiting factor in the development of liver transplantation in Latin America. The liver transplant community in the region should push health care leaders and authorities to comply with the Madrid and Istambul resolutions on organ donation and transplantation. It must pursue fiercely the development of registries to advance the science and quality control of liver transplant activities in Latin America.

Place of liver transplantation in the treatment of hepatocellular carcinoma in the normal liver

Jan Lerut, Hynek Mergental, Delawir Kahn, Luiz Albuquerque, Juan Marrero, Jean Nicolas Vauthey, and Robert J Porte Starzl Abdominal Transplant Unit, St. Luc University Hospital, Catholic University of Louvain, Brussels, Belgium; Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom; Department of Surgery, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa; Digestive Tract Transplantation Unit, Clinic Hospital, University of Sao Paulo, Sao Paulo, Brazil; Department of Hepatology, University of Michigan, Ann Harbor, MI; Liver Surgical Service, MD Anderson Cancer Center, Houston, TX; and Section of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, Groningen, the Netherlands

Venous Thromboembolism Prophylaxis in Liver Surgery

BackgroundAt a recently concluded Americas Hepato-Pancreato-Biliary Association Annual Meeting, a Clinical Practice Guidelines Conference Series was convened with the topic focusing on Venous Thromboembolism (VTE) Prophylaxis in Liver Surgery. The symposium brought together hepatobiliary surgeons from three continents as well as medical experts in hematology and coagulation.MethodsThe content of the discussion included literature reviews, evaluation of multi-institutional VTE outcome data, and examination of practice patterns at multiple high-volume centers.ResultsLiterature review demonstrated that, within gastrointestinal surgery, liver resection patients are at particularly high-risk for VTE. Recent evidence clearly indicates a direct relationship between the magnitude of hepatectomy and postoperative VTE rates, however, the PT/INR does not accurately reflect the coagulation status of the post-hepatectomy patient. Evaluation of available data and practice patterns regarding the utilization and timing of anticoagulant VTE prophylaxis led to recommendations regarding preoperative and postoperative thromboprophylaxis for liver surgery patients.ConclusionsThis conference was effective in consolidating our knowledge of coagulation abnormalities after liver resection. Based on the expert review of the available data and practice patterns, a number of recommendations were developed.

Clinical and pathological evaluation of fibrolamellar hepatocellular carcinoma: a single center study of 21 cases

OBJECTIVES: Fibrolamellar hepatocellular carcinoma is a rare primary malignant liver tumor that differs from conventional hepatocellular carcinoma in several aspects. The aim of this study was to describe the clinical, surgical and histopathological features of fibrolamellar hepatocellular carcinoma and to analyze the factors associated with survival. METHODS: We identified 21 patients with histopathologically diagnosed fibrolamellar hepatocellular carcinoma over a 22-year period. Clinical information was collected from medical records and biopsies, and surgical specimens were reviewed. RESULTS: The median age at diagnosis was 20 years. Most patients were female (67%) and did not have associated chronic liver disease. Most patients had a single nodule, and the median tumor size was 120 mm. Vascular invasion was present in 31% of patients, and extra-hepatic metastases were present in 53%. Fourteen patients underwent surgery as the first-line therapy, three received chemotherapy, and four received palliative care. Eighteen patients had “pure fibrolamellar hepatocellular carcinoma,” whereas three had a distinct area of conventional hepatocellular carcinoma and were classified as having “mixed fibrolamellar hepatocellular carcinoma.” The median overall survival was 36 months. The presence of “mixed fibrolamellar hepatocellular carcinoma” and macrovascular invasion were predictors of poor survival. Vascular invasion was associated with an increased risk of recurrence in patients who underwent surgery. CONCLUSION: Fibrolamellar hepatocellular carcinoma was more common in young female patients without chronic liver disease. Surgery was the first therapeutic option to achieve disease control, even in advanced cases. Vascular invasion was a risk factor for tumor recurrence. The presence of macrovascular invasion and areas of conventional hepatocellular carcinoma were directly related to poor survival.

Phase angle obtained by bioelectrical impedance analysis independently predicts mortality in patients with cirrhosis

AIM To evaluate the prognostic value of the phase angle (PA) obtained from bioelectrical impedance analysis (BIA) for mortality prediction in patients with cirrhosis. METHODS In total, 134 male cirrhotic patients prospectively completed clinical evaluations and nutritional assessment by BIA to obtain PAs during a 36-mo follow-up period. Mortality risk was analyzed by applying the PA cutoff point recently proposed as a malnutrition marker (PA ≤ 4.9°) in Kaplan-Meier curves and multivariate Cox regression models. RESULTS The patients were divided into two groups according to the PA cutoff value (PA > 4.9°, n = 73; PA ≤ 4.9°, n = 61). Weight, height, and body mass index were similar in both groups, but patients with PAs > 4.9° were younger and had higher mid-arm muscle circumference, albumin, and handgrip-strength values and lower severe ascites and encephalopathy incidences, interleukin (IL)-6/IL-10 ratios and C-reactive protein levels than did patients with PAs ≤ 4.9° (P ≤ 0.05). Forty-eight (35.80%) patients died due to cirrhosis, with a median of 18 mo (interquartile range, 3.3-25.6 mo) follow-up until death. Thirty-one (64.60%) of these patients were from the PA ≤ 4.9° group. PA ≤ 4.9° significantly and independently affected the mortality model adjusted for Model for End-Stage Liver Disease score and age (hazard ratio = 2.05, 95%CI: 1.11-3.77, P = 0.021). In addition, Kaplan-Meier curves showed that patients with PAs ≤ 4.9° were significantly more likely to die. CONCLUSION In male patients with cirrhosis, the PA ≤ 4.9° cutoff was associated independently with mortality and identified patients with worse metabolic, nutritional, and disease progression profiles. The PA may be a useful and reliable bedside tool to evaluate prognosis in cirrhosis.

Factors Associated with Mortality and Graft Failure in Liver Transplants: A Hierarchical Approach

Background Liver transplantation has received increased attention in the medical field since the 1980s following the introduction of new immunosuppressants and improved surgical techniques. Currently, transplantation is the treatment of choice for patients with end-stage liver disease, and it has been expanded for other indications. Liver transplantation outcomes depend on donor factors, operating conditions, and the disease stage of the recipient. A retrospective cohort was studied to identify mortality and graft failure rates and their associated factors. All adult liver transplants performed in the state of São Paulo, Brazil, between 2006 and 2012 were studied. Methods and Findings A hierarchical Poisson multiple regression model was used to analyze factors related to mortality and graft failure in liver transplants. A total of 2,666 patients, 18 years or older, (1,482 males; 1,184 females) were investigated. Outcome variables included mortality and graft failure rates, which were grouped into a single binary variable called negative outcome rate. Additionally, donor clinical, laboratory, intensive care, and organ characteristics and recipient clinical data were analyzed. The mortality rate was 16.2 per 100 person-years (py) (95% CI: 15.1–17.3), and the graft failure rate was 1.8 per 100 py (95% CI: 1.5–2.2). Thus, the negative outcome rate was 18.0 per 100 py (95% CI: 16.9–19.2). The best risk model demonstrated that recipient creatinine ≥ 2.11 mg/dl [RR = 1.80 (95% CI: 1.56–2.08)], total bilirubin ≥ 2.11 mg/dl [RR = 1.48 (95% CI: 1.27–1.72)], Na+ ≥ 141.01 mg/dl [RR = 1.70 (95% CI: 1.47–1.97)], RNI ≥ 2.71 [RR = 1.64 (95% CI: 1.41–1.90)], body surface ≥ 1.98 [RR = 0.81 (95% CI: 0.68–0.97)] and donor age ≥ 54 years [RR = 1.28 (95% CI: 1.11–1.48)], male gender [RR = 1.19(95% CI: 1.03–1.37)], dobutamine use [RR = 0.54 (95% CI: 0.36–0.82)] and intubation ≥ 6 days [RR = 1.16 (95% CI: 1.10–1.34)] affected the negative outcome rate. Conclusions The current study confirms that both donor and recipient characteristics must be considered in post-transplant outcomes and prognostic scores. Our data demonstrated that recipient characteristics have a greater impact on post-transplant outcomes than donor characteristics. This new concept makes liver transplant teams to rethink about the limits in a MELD allocation system, with many teams competing with each other. The results suggest that although we have some concerns about the donors features, the recipient factors were heaviest predictors for bad outcomes.

Abdominal wall hernia in cirrhotic patients: emergency surgery results in higher morbidity and mortality

BackgroundPatients with cirrhosis have a high incidence of abdominal wall hernias and carry an elevated perioperative morbidity and mortality. The optimal surgical management strategy as well as timing of abdominal hernia repair remains controversial.MethodsA cohort study of 67 cirrhotic patients who underwent hernia repair during the period of January 1998-December 2009 at the University Hospital of Sao Paulo were included. After meeting study criteria, a total of 56 patients who underwent 61 surgeries were included in the final analysis. Patient characteristics, morbidity (Clavien score), mortality, Child-Turcotte-Pugh score, MELD score, use of prosthetic material, and elective or emergency surgery have been analysed with regards to morbidity and 30-day mortality.ResultsThe median MELD score of the patient population was 14 (range: 6 to 24). Emergency surgery was performed in 34 patients because of ruptured hernia (n = 13), incarceration (n = 10), strangulation (n = 4), and skin necrosis or ulceration (n = 7). Elective surgery was performed in 27 cases. After a multivariable analysis, emergency surgery (OR 7.31; p 0.017) and Child-Pugh C (OR 4.54; p 0.037) were risk factors for major complications. Moreover, emergency surgery was a unique independent risk factor for 30-day mortality (OR 10.83; p 0.028).ConclusionsHigher morbidity and mortality are associated with emergency surgery in advanced cirrhotic patients. Therefore, using cirrhosis as a contraindication for hernia repair in all patients may be reconsidered in the future, especially after controlling ascites and in those patients with hernias that are becoming symptomatic or show signs of possible skin necrosis and rupture. Future prospective randomized studies are needed to confirm this surgical strategy.