ABSTRACT
BACKGROUND: With the emergence of multidrug-resistant infections, healthcare professionals must evaluate the effectiveness of empiric antibiotic treatments. AIMS: To assess the antibiotic susceptibility patterns of microorganisms causing spontaneous infections in patients with cirrhosis and to evaluate the suitability of empiric antibiotic treatments based on major clinical guidelines. METHODS: This cross-sectional study utilized two datasets from prospective studies of patients with cirrhosis and culture-positive spontaneous bacterial infections in Argentina and Uruguay. We estimated susceptibility to commonly used antibiotics and assessed coverage following European and American recommendations. RESULTS: We analyzed 238 episodes of culture-positive spontaneous infections in 229 patients. When implementing the recommendations for empiric treatment of community-acquired spontaneous infections, ceftazidime would result in 39 % coverage, whereas ceftriaxone would reach 70 %. Cefepime, which is not included in the recommendations, would have provided coverage of 74 %. Using ertapenem for nosocomial infections would have only covered 56 % of these episodes, whereas meropenem or imipenem reached 73 % coverage. Only the combination of meropenem or imipenem plus vancomycin would achieve a coverage surpassing 85 % in healthcare-associated or nosocomial spontaneous bacterial infections. CONCLUSIONS: Our study uncovers inadequate coverage in specific clinical scenarios when adhering to recommendations, underscoring the necessity of guidelines based on local epidemiological data.
ABSTRACT
Acetaminophen is a commonly used analgesic and antipyretic drug, which has experienced an increase in its consumption in recent years in our environment. There has also been an increase in the number of accidental and intentional overdoses that were treated by the health system. Its toxicity is dose-dependent and can cause fulminant liver failure, becoming one of the main reasons for liver transplantation in English-speaking countries. The case of a 28-year-old woman with a history of major depression and five previous suicide attempts, who deliberately ingested a significant amount of paracetamol tablets, is here presented. She developed fulminant liver failure and metabolic acidosis, for which she underwent an emergency liver transplant due to the severity of her condition, from which she evolved favorably. The decision to perform a liver transplant in serious cases like this and under a condition of severe psychiatric vulnerability is challenging and must be carefully considered. This particular case illustrates the importance of multidisciplinary care including psychiatric evaluation in patients with acetaminophen poisoning.
El paracetamol es una droga analgésica y antipirética comúnmente utilizada, que ha experimentado un aumento en su consumo en los últimos años en nuestro medio. También se ha observado un incremento en el número de sobredosis accidentales e intencionales que fueron atendidas por el sistema de salud. Su toxicidad es dosis dependiente y puede causar falla hepática fulminante, convirtiéndose en una de las principales razones de trasplante hepático en países angloparlantes. Se presenta el caso de una mujer de 28 años con antecedentes de depresión mayor y cinco intentos de suicidio previos, quien ingirió deliberadamente una cantidad significativa de comprimidos de paracetamol. Desarrolló una falla hepática fulminante y acidosis metabólica, por lo que fue sometida a un trasplante hepático de emergencia debido a la gravedad de su condición evolucionando favorablemente. La decisión de realizar un trasplante hepático en casos graves como este y bajo una condición de vulnerabilidad psiquiátrica grave, es un desafío y debe considerarse cuidadosamente. Este caso en particular ilustra la importancia de la atención multidisciplinaria incluyendo la evaluación psiquiátrica en pacientes con intoxicación por paracetamol.
Subject(s)
Acetaminophen , Analgesics, Non-Narcotic , Liver Failure, Acute , Liver Transplantation , Suicide, Attempted , Humans , Acetaminophen/poisoning , Female , Adult , Liver Failure, Acute/surgery , Liver Failure, Acute/chemically induced , Analgesics, Non-Narcotic/poisoning , Drug OverdoseABSTRACT
RESUMEN Antecedentes: concentrar esta patología hepatobiliar en centros especializados puede permitir bajas cifras de morbimortalidad y mejores resultados alejados. Objetivo: describir las características clínico-patológicas y los resultados de una serie de pacientes operados en los primeros 10 años de una Unidad de Cirugía Hepatobiliar Compleja y Trasplante Hepático (TH), así como la actividad científica y docente de sus integrantes. Materiales y métodos: estudio retrospectivo descriptivo. Se recopiló información de una base de datos prospectiva. Se clasificaron los procedimientos según su complejidad y se analizaron los TH, las hepatectomías y los procedimientos biliares complejos, realizados entre 2013 y 2022. Resultados: sobre 1440 procedimientos quirúrgicos, 832 fueron de alta complejidad (58%). Se realizaron 452 trasplantes hepáticos (TH), 14 (3%) de ellos hepatorrenales; la sobrevida global del trasplante fue de 83%, 77% y 75% a 1, 3 y 5 años, respectivamente. La falla primaria del injerto se observó en 5 casos (1,1%). Se efectuaron 254 hepatectomías: 58 (23%) por patología benigna, 155 (61%) por patología maligna y 41 (16%) en donante vivo relacionado para TH. La morbilidad total fue del 27% y la mortalidad intrahospitalaria de 2%. Se efectuaron 106 derivaciones biliodigestivas: 53 en pacientes con lesión quirúrgica de la vía biliar. La morbilidad a 30 días fue del 42%, en su mayoría complicaciones menores (28%). Además, se realizaron 17 duodenopancreatectomías cefálicas y 3 esplenopancreatectomías. Se realizaron múltiples publicaciones, presentaciones y cursos, y desde 2015 se implementó una residencia posbásica de la especialidad. Conclusión: la concentración de patología hepatobiliar en un centro de alta complejidad permitió alcanzar resultados satisfactorios, comparables con series extranjeras.
ABSTRACT Background: Centralizing hepatobiliary disease in specialized centers can reduce morbidity and mortality rates and improve long-term outcomes. Objective: The aim of the present study was to describe the clinical and pathological features and surgical outcomes of a series of patients operated on in the Hepatobiliary Surgery and Liver Transplantation Unit of Hospital El Cruce during its first 10 years, as well as the scientific and educational activity of its members. Material and methods: We conducted a descriptive and retrospective study. The information was retrieved from a prospective database. The procedures were classified according to their complexity. An analysis was conducted on liver transplantations (LTs), liver resections and complex biliary procedures, performed from 2013 to 2022. Results: Of 1449 surgical procedures, 832 were high-complexity interventions (58%). A total of 452 LTs were performed, 14 (3%) were combined liver and kidney transplantations; overall transplant survival was 83%, 77% and 75% at 1, 3 and 5 years, respectively. Primary graft dysfunction was observed in 5 cases (1.1%). There were 254 liver resections; 58 cases (23%) were related to benign liver diseases, 155 (61%) to malignancies, and 41 (16%) were associated with living donor transplants. Overall morbidity was 27% and in-hospital mortality was 2%. A total of 106 bilio-digestive bypass procedures were carried out, 53 in patients with bile duct injury. Thirty-day morbidity was 42%, and most cases were minor complications (28%). Other procedures included 17 cephalic pancreaticoduodenectomies and 3 splenectomies and distal pancreatectomies. We have published numerous papers, delivered presentations and courses, and implemented a fellowship program in the specialty since 2015. Conclusion: Centralizing hepatobiliary diseases at a high-complexity center led to comparable outcomes with those reported in international series.
ABSTRACT
Solid organ transplant recipients (SOTR) commonly develop an unsatisfactory humoral response to vaccines compared to immunocompetent individuals (IC). We have previously evaluated the humoral response in liver transplant recipients (LTR) who received two-dose vaccines against SARS-CoV-2 and reported that 38 % of LTR did not produce anti-Spike antibodies. Thus, we set out to evaluate the humoral response after the third dose of SARS-CoV-2 vaccines. For this purpose, samples from a cohort of 81 LTR and 27 IC were extracted between 21 and 90 days after the third dose. Serology for anti-Spike IgG antibodies and neutralizing antibodies against Wuhan, Delta and Omicron variants were evaluated. We found that 73.5 % of LTR were responders for anti-Spike IgG, while all the IC mounted a measurable response. LTR who responded to the third dose showed significantly lower anti-Spike IgG levels and neutralizing antibodies than IC. We found that there is less neutralization in LTR compared to IC across all variants. Specifically, the neutralization titers in both groups decrease when encountering the Delta variant, and this decline is even more pronounced with the Omicron variant, compared to the Wuhan variant. Furthermore, we identified that the use of high doses of mycophenolate and advanced age were factors that negatively affected the development of anti-Spike IgG antibodies. Regarding vaccine regimes, the regime viral vector/mRNA/mRNA elicited significantly higher responses in LTR compared to other vaccine schemes. In addition to the recommended and necessary booster doses in this population, strategies that achieve adequate immunization should be evaluated.
Subject(s)
COVID-19 , Liver Transplantation , Humans , COVID-19 Vaccines , COVID-19/prevention & control , SARS-CoV-2 , Antibodies, Neutralizing , RNA, Messenger , Transplant Recipients , Immunoglobulin G , Antibodies, ViralABSTRACT
INTRODUCTION AND OBJECTIVES: South America is one of the regions with the highest rates of non-alcoholic fatty liver disease (NAFLD). This study aimed to assess the prevalence and severity of NAFLD in suburban Argentina. PATIENTS AND METHODS: The study involved a general community cohort of 993 subjects evaluated sequentially with a comprehensive lifestyle questionnaire, laboratory testing, abdominal ultrasound (US) and transient elastography with XL probe. NAFLD was diagnosed according to standard criteria. RESULTS: The prevalence of NAFLD by the US was 37.2% (326/875) overall, 50.3% in subjects with overweight/obesity, 58.6% with hypertriglyceridemia, 62.3% with diabetes/hyperglycemia and 72.1% with all three risk factors. Male gender (OR 1.42, 95% CI 1.03-1.47, p = 0.029), age (50-59 years: OR 1.98, 95 CI 1.16-3.39, p = 0.013 and ≥60 years: OR 1.86, 95% CI 1.13-3.09, p = 0.015), BMI (25-29: OR 2.87, 95% CI 1.86-4.51, p<0.001 and ≥30: OR 9.57, 95% CI 6.14-15.20, p<0.001), diabetes/hyperglycemia (OR 1.65, 95% CI 1.05-2.61, p = 0.029) and hypertriglyceridemia (OR 1.73, 95% CI 1.20-2.48, p = 0.002) were independent predictors of NAFLD. Among patients with steatosis, 22.2% (69/311) had ≥F2 fibrosis (overweight 25%, hypertriglyceridemia 32%, diabetes/hyperglycemia 34%). BMI (OR 5.22, 95% CI 2.64-11.74, p<0.001), diabetes/hyperglycemia (OR 2.12, 95% CI 1.05-4.29, p = 0.04) and hypertriglyceridemia (OR 1.94, 95% CI 1.03-3.68, p = 0.040) were independent predictors of liver fibrosis. CONCLUSIONS: This general population study from Argentina showed a high prevalence of NAFLD. Significant liver fibrosis was present in 22% of subjects with NAFLD. This information adds to the existing knowledge of NAFLD epidemiology in Latin America.
Subject(s)
Diabetes Mellitus , Hyperglycemia , Hypertriglyceridemia , Non-alcoholic Fatty Liver Disease , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/epidemiology , Overweight , Prevalence , Argentina/epidemiology , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/epidemiology , Diabetes Mellitus/etiology , Hyperglycemia/complications , Hyperglycemia/pathology , Hypertriglyceridemia/complications , Hypertriglyceridemia/pathology , Liver/pathologyABSTRACT
This study aimed to evaluate the nutritional and bioeconomic potential of rehydrated ground grain corn silage (RGGCS), at different storage times associated with proportions of concentrates for better starch utilization by lambs. Forty Dorper-Santa Inês crossbred lambs were used, with an average body weight of 24 ± 3.9 kg, and an average age of 90 days. The lambs were feedlot for 63 days in experiment design completely randomized, with eight repetitions and five experimental diets: Diet 1: 850 g/kg concentrate including dry ground corn; diet 2: 850 g/kg concentrate including RGGCS ensiled for 45 days; diet 3: 650 g/kg concentrate including RGGCS ensiled for 90 days; diet 4: 650 g/kg concentrate including RGGCS ensiled for 45 days; diet 5: 850 g/kg concentrate including RGGCS ensiled for 45 days. As roughage, silage corn whole plant. Starch intake was higher (P < 0.05) with the dry ground corn diet; however, digestibility was lower (P < 0.05) for most nutrients compared to the RGGCS diet. A smaller amount of starch in the feces of animals that received the RGGCS diet was found. A diet with 850 g/kg of concentrate, including RGGCS ensiled for 45 days, generates higher net income, increases nutrient intake, and could be an alternative during the fluctuation of corn prices.
Subject(s)
Silage , Zea mays , Animal Nutritional Physiological Phenomena , Animals , Digestion , Edible Grain , Sheep , Sheep, Domestic , Silage/analysis , StarchABSTRACT
Knowledge of the immunogenicity of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in liver transplant recipients (LTRs) is mainly limited to messenger RNA (mRNA)-based types. We aimed to evaluate the humoral response in LTRs and to address the use of different doses of mycophenolate (MMF) on the probability of developing anti-spike immunoglobulin G (IgG). In this prospective cohort study, SARS-CoV-2 anti-spike IgG, neutralizing antibodies (NAs), and nucleocapsid protein (N) were evaluated in LTRs and healthy volunteers 21-90 days after receiving the second vaccine dose of either ChAdOx1 (AstraZeneca), rAd26-rAd5 (Sputnik V), inactivated BBIBP-CorV (Sinopharm), or the heterologous combination rAd26/mRNA-1273 (Sputnik V/Moderna). We collected information regarding clinical data and vaccine side effects. After excluding three LTRs due to a positive N test, 120 LTRs and 27 controls were analyzed. No significant differences were found among groups. Overall, 24 (89%) controls and 74 (62%) LTRs were positive for anti-spike IgG (p = 0.007). Among LTRs, those immunized with rAd26/mRNA-1273 presented significantly higher positive serology and NAs when compared with the homologous regimens (91% vs. 55%, p = 0.001; and 1182 IU/ml vs. 446 IU/ml, p = 0.002; respectively). In the multivariate analysis, humoral response was significantly reduced in LTRs who received higher doses of MMF (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.03-0.3; p < 0.001) and with increased BMI (OR, 0.4; 95% CI, 0.2-0.7; p = 0.005); and it was significantly higher in those immunized with rAd26/mRNA-1273 (OR, 13.1; 95% CI, 2.3-72.9; p = 0.003). In LTRs anti-spike IgG concentrations showed a very good correlation with NA titers (R2 = 0.949; 95% CI, 0.919-0.967; p < 0.001). No serious adverse events were reported in either group. Conclusion: In LTRs, rAd26/mRNA-1273 was independently associated with higher antibody response. Future studies are necessary to evaluate whether combining different vaccine platforms and MMF reduction may lead to a better booster response.
Subject(s)
COVID-19 , Liver Transplantation , Viral Vaccines , Adenoviridae/genetics , Antibodies, Neutralizing , Humans , Immunoglobulin G , Nucleocapsid Proteins/genetics , Prospective Studies , RNA, Messenger , SARS-CoV-2ABSTRACT
INTRODUCTION AND OBJECTIVES: In 1999, a population-based survey showed a 5.6 % (102/1832) prevalence of HCV infection in O'Brien, a small rural town of Argentina. The aim of this study was to assess the impact of screening, clinical evaluation and antiviral therapy on elimination of HCV after 20 years of follow-up. PATIENTS AND METHODS: HCV+ subjects (n=102) underwent clinical, biochemical and histological evaluation to assess the presence and severity of liver disease. Antiviral therapy included pegylated interferon + ribavirin in 2005 and direct antiviral agents from 2017. RESULTS: All viremic subjects (n=84) had genotype 1b with 90%-97.5% sequence homology scores, suggesting the existence of a common source of infection (use of unsafe injections administered by the same health professional). Liver biopsy (n=55) showed chronic hepatitis in all patients. The prevalence of cirrhosis was 28% overall (29/102) and 34.5% among viremic patients. Sustained virological response (SVR) was obtained in 20/34 (59%) patients treated with interferon. From 2005 to 2017, when oral antivirals became available 37/50 untreated patients died. Median age of this group in 2005 was 67 years. Six interferon non-responders and five naive subjects received direct antiviral agents and all developed SVR. Only 1/31 patient (3.2%) with SVR died and none developed decompensated cirrhosis or HCC. In 2019, a new population-based study showed that the prevalence of HCV in O'Brien decreased 20-fold, from 5.6% to 0.28% (3/1070). CONCLUSIONS: Despite the high mortality rate precluding timely access to direct antiviral agents, the O'Brien Project is a good example of HCV micro-elimination studies.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis C, Chronic , Hepatitis C , Liver Neoplasms , Aged , Antiviral Agents/adverse effects , Argentina/epidemiology , Carcinoma, Hepatocellular/epidemiology , Disease Outbreaks , Drug Therapy, Combination , Follow-Up Studies , Hepacivirus/genetics , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Humans , Liver Neoplasms/epidemiology , Ribavirin/therapeutic useABSTRACT
BACKGROUND & AIMS: Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined by a model for end-stage liver disease (MELD) score >20. However, there are patients who may be too sick to benefit from therapy. Herein, we aimed to identify the range of MELD scores within which steroids are effective for AH. METHODS: We performed a retrospective, international multicenter cohort study across 4 continents, including 3,380 adults with a clinical and/or histological diagnosis of AH. The main outcome was mortality at 30 days. We used a discrete-time survival analysis model, and MELD cut-offs were established using the transform-the-endpoints method. RESULTS: In our cohort, median age was 49 (40-56) years, 76.5% were male, and 79% had underlying cirrhosis. Median MELD at admission was 24 (19-29). Survival was 88% (87-89) at 30 days, 77% (76-78) at 90 days, and 72% (72-74) at 180 days. A total of 1,225 patients received corticosteroids. In an adjusted-survival-model, corticosteroid use decreased 30-day mortality by 41% (hazard ratio [HR] 0.59; 0.47-0.74; p <0.001). Steroids only improved survival in patients with MELD scores between 21 (HR 0.61; 0.39-0.95; p = 0.027) and 51 (HR 0.72; 0.52-0.99; p = 0.041). The maximum effect of corticosteroid treatment (21-30% survival benefit) was observed with MELD scores between 25 (HR 0.58; 0.42-0.77; p <0.001) and 39 (HR 0.57; 0.41-0.79; p <0.001). No corticosteroid benefit was seen in patients with MELD >51. The type of corticosteroids used (prednisone, prednisolone, or methylprednisolone) was not associated with survival benefit (p = 0.247). CONCLUSION: Corticosteroids improve 30-day survival only among patients with severe AH, especially with MELD scores between 25 and 39. LAY SUMMARY: Alcohol-associated hepatitis is a condition where the liver is severely inflamed as a result of excess alcohol use. It is associated with high mortality and it is not clear whether the most commonly used treatments (corticosteroids) are effective, particularly in patients with very severe liver disease. In this worldwide study, the use of corticosteroids was associated with increased 30-day, but not 90- or 180-day, survival. The maximal benefit was observed in patients with an MELD score (a marker of severity of liver disease; higher scores signify worse disease) between 25-39. However, this benefit was lost in patients with the most severe liver disease (MELD score higher than 51).
Subject(s)
Alcohol Drinking/adverse effects , Hepatitis/drug therapy , Steroids/administration & dosage , Time Factors , Adult , Alcohol Drinking/drug therapy , Alcohol Drinking/physiopathology , Cohort Studies , Female , Hepatitis/etiology , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Steroids/therapeutic useABSTRACT
INTRODUCCIÓN el conocimiento de la inmunogenicidad de las vacunas contra el SARS-CoV-2 en receptores de trasplante hepático (LTR) se limita principalmente a los tipos basados en ARNm.Nuestro objetivo fue evaluar la respuesta humoral en LTR y abordar el uso de diferentes dosis de micofenolato (MMF) sobre la probabilidad de desarrollar IgG anti-Spike. MÉTODOS en este estudio de cohorte prospectivo, evaluamos la respuesta anti-Spike IgG SARS-CoV- 2, los anticuerpos neutralizantes (NA) y la proteína de la nucleocápside (N) en LTR y voluntarios sanos 21-90 días después de recibir la segunda dosis de la vacuna, ya sea ChAdOx1, rAd26-rAd5, BBIBP-CorV inactivado o la combinación heteróloga rAd26/mRNA-1273. Recopilamos información sobre datos clínicos y efectos secundarios de la vacuna. RESULTADOS Después de excluir 3 LTR debido a una prueba N positiva, se analizaron 120 LTR y 27 controles. No se encontraron diferencias significativas entre los grupos. En total, 24 (89%) controles y 74 (62%) LTR desarrollaron IgG anti-Spike (p=0,007) Entre los LTR, los inmunizados con rAd26/mRNA 1273 presentaron serología positiva y NA significativamente más altas en comparación con los regímenes homólogos (91% frente a 55%; p=0,001 y 1182 UI/ml frente a 446 UI/ml, p=0,002;respectivamente). En el análisis multivariado, la respuesta humoral se redujo significativamente e LTR que recibieron dosis más altas de MMF [OR0,1 (0,03-0,3); p<0,001] y con IMC elevado [OR 0,4 (0,2-0,7); p=0,005]; y fue significativamente mayor en los inmunizados con rAd26/mRNA-1273 [OR 13,1 (2,3-72,9); p=0,003]. En los LTR, las concentraciones de IgG anti-Spike mostraron una muy buena correlación con los títulos de NA [p<0,001]. DISCUSIÓN en LTR, rAd26/mRNA-1273 se asoció de forma independiente con una mayor respuesta de anticuerpos. Se necesitan estudios futuros para evaluar si la combinación de diferentes plataformas de vacunas y la reducción de MMF puede conducir a una mejor respuesta de refuerzo.
Subject(s)
Vaccines , COVID-19 , Liver TransplantationABSTRACT
The A.A.E.E.H has developed this guideline for the best care of patients with hepatocellular carcinoma (HCC) from Argentina. It was done from May 2018 to March 2020. Specific clinical research questions were systematically searched. The quality of evidence and level of recommendations were organized according to GRADE. HCC surveillance is strongly recommended with abdominal ultrasound (US) every six months in the population at risk for HCC (cirrhosis, hepatitis B or hepatitis C); it is suggested to add alpha-feto protein (AFP) levels in case of inexeperienced sonographers. Imaging diagnosis in patients at risk for HCC has high specificity and tumor biopsy is not mandatory. The Barcelona Clinic Liver Cancer algorithm is strongly recommended for HCC staging and treatment-decision processes. Liver resection is strongly recommended for patients without portal hypertension and preserved liver function. Composite models are suggested for liver transplant selection criteria. Therapies for HCC with robust clinical evidence include transarterial chemoembolization (TACE) and first to second line systemic treatment options (sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab). Immunotherapy with nivolumab and pembrolizumab has failed to show statistical benefit but the novel combination of atezolizumab plus bevacizumab has recently shown survival benefit over sorafenib in frontline.
Subject(s)
Carcinoma, Hepatocellular/therapy , Decision Support Techniques , Liver Neoplasms/therapy , Medical Oncology/standards , Neoplasm Staging/standards , Algorithms , Argentina , Biopsy/standards , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Clinical Decision-Making , Consensus , Evidence-Based Medicine/standards , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Predictive Value of Tests , Risk Assessment , Risk Factors , Treatment Outcome , Ultrasonography/standardsABSTRACT
INTRODUCTION AND AIM: Liver transplantation (LT) for acute liver failure (ALF) still has a high early mortality. We aimed to evaluate changes occurring in recent years and identify risk factors for poor outcomes. MATERIAL AND METHODS: Data were retrospectively obtained from the Argentinean Transplant Registry from two time periods (1998-2005 and 2006-2016). We used survival analysis to evaluate risk of death. RESULTS: A total of 561 patients were listed for LT (69% female, mean age 39.5±16.4 years). Between early and later periods there was a reduction in wait-list mortality from 27% to 19% (p<0.02) and 1-month post-LT survival rates improved from 70% to 82% (p<0.01). Overall, 61% of the patients underwent LT and 22% died on the waiting list. Among those undergoing LT, Cox regression analysis identified prolonged cold ischemia time (HR 1.18 [1.02-1.36] and serum creatinine (HR 1.31 [1.01-1.71]) as independent risk factors of death post-LT. Etiologies of ALF were only available in the later period (N=363) with indeterminate and autoimmune hepatitis accounting for 28% and 26% of the cases, respectively. After adjusting for age, gender, private/public hospital, INR, creatinine and bilirubin, and considering LT as the competing event, indeterminate etiology was significantly associated with death (SHR 1.63 [1.06-2.51] and autoimmune hepatitis presented a trend to improved survival (SHR 0.61 [0.36-1.05]). CONCLUSIONS: Survival of patients with ALF on the waiting list and after LT has significantly improved in recent years. Indeterminate cause and autoimmune hepatitis were the most frequent etiologies of ALF in Argentina and were associated with mortality.
Subject(s)
Liver Failure, Acute/surgery , Liver Transplantation , Waiting Lists , Adult , Argentina/epidemiology , Decision Support Techniques , Female , Graft Survival , Health Status , Health Status Indicators , Hepatitis, Autoimmune/diagnosis , Hepatitis, Autoimmune/mortality , Humans , Liver Failure, Acute/diagnosis , Liver Failure, Acute/mortality , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Male , Middle Aged , Registries , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Tissue and Organ Procurement , Treatment Outcome , Waiting Lists/mortality , Young AdultABSTRACT
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Most studies addressing the epidemiology of HCC originate from developed countries. This study reports the preliminary findings of a multinational approach to characterize HCC in South America. METHODS: We evaluated 1336 HCC patients seen at 14 centres in six South American countries using a retrospective study design with participating centres completing a template chart of patient characteristics. The diagnosis of HCC was made radiographically or histologically for all cases according to institutional standards. Methodology of surveillance for each centre was following AASLD or EASL recommendations. RESULTS: Sixty-eight percent of individuals were male with a median age of 64 years at time of diagnosis. The most common risk factor for HCC was hepatitis C infection (HCV, 48%), followed by alcoholic cirrhosis (22%), Hepatitis B infection (HBV, 14%) and NAFLD (9%). We found that among individuals with HBV-related HCC, 38% were diagnosed before age 50. The most commonly provided therapy was transarterial chemoembolization (35% of HCCs) with few individuals being considered for liver transplant (<20%). Only 47% of HCCs were diagnosed during surveillance, and there was no difference in age of diagnosis between those diagnosed incidentally vs by surveillance. Nonetheless, being diagnosed during surveillance was associated with improved overall survival (P = .01). CONCLUSIONS: Our study represents the largest cohort to date reporting characteristics and outcomes of HCC across South America. We found an important number of HCCs diagnosed outside of surveillance programmes, with associated increased mortality in those patients.
Subject(s)
Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/epidemiology , Liver Neoplasms/therapy , Aged , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/mortality , Early Detection of Cancer/methods , Female , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Male , Middle Aged , Predictive Value of Tests , Preliminary Data , Retrospective Studies , Risk Factors , South America/epidemiology , Treatment OutcomeSubject(s)
Carcinoma, Hepatocellular/epidemiology , Hepatitis B, Chronic/complications , Liver Neoplasms/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Demography , Female , Humans , International Cooperation , Male , Middle Aged , Retrospective Studies , Risk Factors , South America/epidemiology , Young AdultABSTRACT
OBJECTIVES: Previous studies have reported reduced tacrolimus dose-adjusted exposure in individuals expressing the CYP3A5*1 allele (reference single nucleotide polymorphism identification number 776746). However, results on patients from South America are scarce. The objective of this study was to investigate the influence of CYP3A5 and MDR1 allelic variants and their correlation on the pharmacokinetics of tacrolimus and a modified release formulation of tacrolimus in stable patients with liver transplant. MATERIALS AND METHODS: This was a prospective, single center, open-label study. Included patients were ≥ 18 years old and receiving a stable dose of tacrolimus for at least 6 months. Patients receiving stable treatment of twice daily tacrolimus were switched to a once-daily dose of modified release tacrolimus, on a milligram-to-milligram basis, with the modified release formulation administered for at least 4 weeks. Blood levels of tacrolimus were obtained before and 1 month after treatment was switched to the modified release formulation. RESULTS: The frequency of the intron 3 allelic variant of the CYP3A5 isoform (G-to-A substitution at nucleotide 6986) in recipients was 16.6% and 25% in donors. Dose levels of tacrolimus and the modified formulation were significantly higher in donors and recipients who expressed CYP3A5 versus donors and recipients who did not express this allele. In addition, patients who received a liver from a donor expressing CYP3A5 had significantly lower trough concentrations of tacrolimus and the modified formulation. CYP3A5 expression in the donor liver affected tacrolimus (40.46%, P = .001) and modified formulation (37.56%, P = .001) variability. No association was found between the ABCB1 genotype and levels of tacrolimus or its modified formulation. CONCLUSIONS: Our data suggest that CYP3A5*1 in either the donor or recipient resulted in higher mean daily doses of tacrolimus or its modified formulation to achieve target drug exposure in liver transplant patients.
Subject(s)
Cytochrome P-450 CYP3A/genetics , Immunosuppressive Agents/pharmacokinetics , Liver Transplantation , Polymorphism, Genetic , Tacrolimus/pharmacokinetics , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Adult , Aged , Argentina , Biotransformation , Cytochrome P-450 CYP3A/metabolism , Delayed-Action Preparations , Drug Administration Schedule , Drug Dosage Calculations , Drug Monitoring , Female , Gene Frequency , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/blood , Male , Middle Aged , Pharmacogenetics , Phenotype , Prospective Studies , Tacrolimus/administration & dosage , Tacrolimus/bloodABSTRACT
BACKGROUND & AIMS: Robust clinical data evaluating fibrosis progression in hepatitis C virus (HCV) liver transplant patients receiving an mTOR inhibitor vs. calcineurin inhibitor (CNI) are lacking. To evaluate fibrosis progression in maintenance liver transplant patients receiving everolimus- or CNI-based immunosuppression. METHODS: In a randomised, multicentre, open-label study, 43 maintenance liver transplant patients with recurrent HCV infection were randomised to continue CNI-based immunosuppression or switch to everolimus. RESULTS: For patients with biopsy data at month 12, mean Ishak-Knodell fibrosis score at baseline was 2.6 ± 0.9 (n = 14) with everolimus vs. 1.9 ± 1.1 (n = 18) with CNI (P = 0.043), and 1.9 ± 1.2 vs. 2.2 ± 1.3 at month 12. Ishak-Knodell fibrosis score decreased from baseline to month 12 by a mean of -0.7 ± 1.1 with everolimus, but increased by 0.2 ± 1.2 with CNI (P = 0.046). No acute rejection or graft losses occurred up to month 12. Estimated GFR at month 12 was 65.6 ml/min/1.73 m² with everolimus and 62.2 ml/min/1.73 m² with CNI [mean difference 3.4 ml/min/1.73 m² compared to CNI control group, 95% CI -4.9, 11.8 ml/min/1.73 m², P = 0.411 (analysis of covariance adjusting for baseline GFR)]. Adverse events occurred in 95.5% of everolimus patients and 71.4% of CNI patients (serious adverse events 31.8% and 0.0%, respectively). Adverse events led to everolimus discontinuation in five patients (22.7%). CONCLUSIONS: This exploratory study suggests that conversion from CNI to everolimus reduces progression of liver fibrosis, and preserves renal function without jeopardising efficacy in liver transplant recipients with recurrent HCV, but is associated with a higher incidence of adverse events and serious adverse events. These preliminary findings merit examination in a larger trial.