Juan Manuel Sánchez-Hidalgo

Impact of donor graft steatosis on overall outcome and viral recurrence after liver transplantation for hepatitis C virus cirrhosis

The aim of this study was to determine the influence of donor graft steatosis on overall outcome, viral recurrence, and fibrosis progression in orthotopic liver transplantation (OLT) for hepatitis C virus (HCV) cirrhosis. One hundred twenty patients who underwent OLT for HCV cirrhosis between 1995 and 2005 were included in the study. Donor steatosis was categorized as absent (0%‐10%; n = 40), mild (10%‐30%; n = 32), moderate (30%‐60%; n = 29), or severe (>60%; n = 19). A Cox multivariate analysis for marginal donor variables and a Model for End‐Stage Liver Disease index were performed. Fibrosis evolution was analyzed in liver biopsies (fibrosis < 2 or ≥2) 3, 6, and 12 months post‐OLT and in the late post‐OLT period. Fifty‐six grafts were lost (46%). The survival of the grafts was inversely proportional to donor liver steatosis: 82%, 72%, and 72% at 1, 2, and 3 years post‐OLT in the absence of steatosis; 73%, 63%, and 58% with mild steatosis; 74%, 62%, and 43% with moderate steatosis; and 62%, 49%, and 42% with severe steatosis (P = 0.012). HCV recurrence was earlier and more frequent in recipients with steatosis > 30% (46% versus 32% at 3 months, P = 0.017; 58% versus 43% at 6 months, P = 0.020; 70% versus 56% at 12 months, P = 0.058; and 95% versus 69% at 3 years post‐OLT, P = 0.0001). Graft survival was lower in alcoholic liver disease recipients versus HCV recipients when steatosis was >30% at 3, 6, and 12 months post‐OLT (P = 0.042) but not when steatosis was <30% (P = 0.53). A higher fibrosis score was obtained 3 months post‐OLT (P = 0.033), 6 months post‐OLT (P = 0.306), 12 months post‐OLT (P = 0.035), and in the late post‐OLT period (P = 0.009). In conclusion, donor graft steatosis influences the outcome of OLT for HCV cirrhosis. HCV recurrence is more frequent and earlier in recipients of moderately and severely steatotic livers. Fibrosis evolution is higher when graft steatosis is >30%. OLT with >30% steatotic donor livers should be precluded in HCV recipients. Liver Transpl 15:37–48, 2009.

Impact of age on liver regeneration response to injury after partial hepatectomy in a rat model.

BACKGROUND Liver resection is a feasible treatment for multiple liver diseases. There is no evidence about the impact of age on liver regeneration. OBJECTIVE To assess the effect of age on liver regeneration in an experimental in vivo animal model of 70%-partial hepatectomy. METHODS Forty young (Y) and old (O) Wistar male rats (n = 80) were distributed into four groups [controls (C), sham operated (SO), hepatectomy 6 h (H6), and 48 h (H48)]. Different morphometric and biochemical factors, oxidative and nitrosative stress, lipid peroxidation, cytokines kinetics, and histopathologic tissular parameters were determined. RESULTS Early postoperative mortality was higher in aged rats (P = 0.049). Morphometric determinations, liver regeneration index, and total volume weight were favorable to young rats. Serum transaminase levels were higher in aged rats. Parameters of necrosis (measured by histopathologic injury [HI: 0-I-II-III]), regeneration (measured by bromodeoxyuridine-BrdU incorporation) and apoptosis (determined by the TDT-mediated dUTP nick end labeling-TUNEL) were well-synchronized in young rats. Parameters of oxidative stress such as reduced (GSH), oxidized (GSSG) glutathione and lipid peroxidation (measured by hepatic malondialdehyde -MDA-) were lower in young animals throughout the studied period. Nitrosative stress measured by nitric oxide (NO) end-products was higher in late stages in resected old rats. Pro-inflammatory cytokines (TNF- α) reached higher and earlier levels in aged rats while pro-regenerative cytokines (IL-6) were significantly higher in early stages for young rats and in late stages for aged rats. The levels of TGF-β were higher in young rats. CONCLUSION Liver regeneration is delayed and reduced in aged animals submitted to liver resection.

Model for end-stage liver disease can predict very early outcome after liver transplantation.

Postoperative Model for End-stage Liver Disease (MELD) values have never been assessed to predict very early (<1 week) death after liver transplantation (OLT). We retrospectively reviewed 275 consecutive OLTs performed in 252 recipients reported in a prospective database. We calculated the MELD score (pre-MELD) and consecutive postoperative MELD (post-MELD) scores computed daily during the first postoperative week and on days 15 and 30 after OLT. Post-MELD scores from nonsurviving recipients displayed on a scatterplot of immediate probability of death were adjusted to the best goodness-of-fit curve, and, finally, depicted graphically as a receiver operating characteristic (ROC) curve. Nonsurviving recipients showed higher post-MELD scores: day 1: 23.5 versus 16.6 (P = .05); day 3: 25.1 versus 12.5 (P = .000); day 5: 25.7 versus 11.8 (P = .000); and day 7: 22.1 versus 10.2 (P = .000). Overall comparisons were performed using a time-dependent general linear regression model, revealing higher post-MELD scores for nonsurviving recipients, irrespective of postoperative time (P = .002). The best goodness-of-fit curve was displayed when adjusting to a theoretical exponential regression curve calculated as follows: Probability of dying within the first week (%) = 3.36 x e(0.079 x (post-MELD)) (r = .89; P = .000). The area under the ROC curve was 0.783 (95% confidence interval, 0.630-0.935; P = .001). The model had a positive predictive value of 82.3%, a negative predictive value of 33.1%, and an accuracy of 79.2%. In conclusion, this study corroborated the suggestion that the MELD score may serve as a reliable tool to assess very early death after OLT.

Establishment of a Pediatric Liver Transplantation Program: Experience With 100 Transplantation Procedures

OBJECTIVE To analyze the primary factors that influence the development and consolidation of a pediatric liver transplantation program. PATIENTS AND METHODS This was a retrospective study of 100 liver transplantation procedures performed in 84 pediatric patients between May 1990 and November 2007. The male-female ratio was 40:60. Mean (SD) age was 5 years (40 patients were younger than 2 years); cold ischemia time was 7.10 (3.1) hours; surgery time was 5.2 (2.2) hours; and time on the waiting list for transplantation was 75 (range, 1-1012) days. Indications for transplantation included cholestatic disease (43%), acute hepatic failure (AHF; 34%), metabolic disorders (14%), and cirrhosis (9%). Transplanted organs included 3 split grafts, 29 partial grafts, and 8 living-donor grafts. RESULTS Mean graft survival was 70.4%, 59.2%, and 58.1% at 1, 3, and 5 years, respectively. Factors that influenced graft outcome were age younger than 2 years; surgery time more than 6 hours; and AHF vs cholestatic disease, metabolic disorders, and cirrhosis. There were no significant differences in long-term (51% vs 59%) and short-term (71% vs 70%) graft survival between procedures performed in 1990-1998 compared with those performed in 1999-2007; however, there was a higher percentage (P = .005) of recipients at high risk (age younger than 2 years or with AHF) in the later period. All data were consistent with those of the European Liver Transplant Registry 2007. CONCLUSIONS A pediatric liver transplantation program can be established by a group experienced in liver transplantation.

Factors Affecting Survival and Tumor Recurrence in Patients Transplanted for Hepatocellular Carcinoma and Coexistent Hepatitis C Virus

A better understanding of tumor factors influencing patient and graft survival and recurrence of hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) cirrhosis may be useful to maximize the benefits of liver transplantation (OLT). Sixty-three adults underwent OLT for end-stage liver disease secondary to HCV with concomitant HCC. The outcome measures were patient and graft survival, as well as recurrence-free survival, computed using a stepwise Cox proportional hazards regression analysis. Kaplan-Meier 1-, 3-, and 5-year patient survival rates were 82%, 80%, and 69%, respectively, they were better for incidentally discovered HCC compared with preoperatively diagnosed HCC (P = .04). The overall recurrence-free survival rates were 81%, 76%, and 61% at 1, 3, and 5 years, respectively. Univariate analysis showed that nonincidental HCC (P = .04), pTNM stage (P = .012) and vascular invasion (P = .003) correlated with recipient mortality. Vascular invasion (odds ratio [OR] = 2.12; P = .001) and pTNM (OR = 1.50; P = .008) were independent predictors of overall survival. A combination of tumor vascular invasion with advanced pTNM was associated with a dismal prognosis (log-rank = 21.89; P = .0001). Tumor grading (OR = 1.2; P = .04), pTNM (OR = 3.7; P = .001) and vascular invasion (OR = 1.6; P = .002) were independent predictors of recurrence. In conclusion, advanced pTNM and the presence of vascular invasion are strong predictors of poor survival and tumor recurrence.

Prediction Model to Discard A Priori Liver Allografts

BACKGROUND The use of expanded criteria for donors to expand the donor pool has increased the number of discarded liver grafts in situ. The aim of our study was to elaborate a prediction model to reduce the percentage of liver grafts discarded before the procuring team is sent out. METHODS We analyzed the donor factors of 244 evaluated candidates for liver donation. We performed a multiple logistic regression to evaluate the probability of liver grafts discarded (PD). RESULTS The PD was determined by use of 3 variables: age, pathological ultrasonography, and body mass index >30. The area under curve was 82.7%, and, for a PD of 70%, the false-positive probability was 1.2%. CONCLUSIONS We have created a useful clinical prediction model that could avoid up to 20% of discarded liver grafts.

Gastrointestinal stromal tumors: A multidisciplinary challenge

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors located in the alimentary tract. Its usual manifestation is gastrointestinal bleeding. However, small asymptomatic lesions are frequently detected as incidental finding. Characteristically, most GISTs (> 95%) are positive for the KIT protein (CD117) by IHC staining and approximately 80%-90% of GISTs carry a mutation in the c-KIT or PDGFRA genes. Mutational analysis should be performed when planning adjuvant and neoadjuvant therapy, due to its possible resistance to conventional treatment. The arise of tyrosine kinase inhibitor has supposed a revolution in GISTs treatment being useful as adjuvant, neoadjuvant or recurrence disease treatment. That is why a multidisciplinary approach to this disease is required. The correct characterization of the tumor at diagnosis (the diagnosis of recurrences and the evaluation of the response to treatment with tyrosine kinase inhibitors) is fundamental for facing these tumors and requires specialized Endoscopist, Radiologists and Nuclear Medicine Physician. Surgery is the only potentially curative treatment for suspected resectable GIST. In the case of high risk GISTs, surgery plus adjuvant Imatinib-Mesylate for 3 years is the standard treatment. Neoadjuvant imatinib-mesylate should be considered to shrink the tumor in case of locally advanced primary or recurrence disease, unresectable or potentially resectable metastasic tumors, and potentially resectable disease in complex anatomic locations to decrease the related morbidity. In the case of Metastatic GIST under Neoadjuvant treatment, when there are complete response, stable disease or limited disease progression, complete cytoreductive surgery could be a therapeutic option if feasible.

Hepatectomía derecha por actinomicosis hepática

Paciente de 26 años de edad, testigo de Jehová, que acude por cuadro febril de 12 días de evolución acompañado de tos productiva, expectoración blanquecina, sensación disneica, distensión abdominal y edema de miembros inferiores. Su analítica al ingreso presentó: fosfatasa alcalina, 243 U/l; gammaglutamiltransferasa, 173 U/l; AST, 67 U/l; ALT, 110 U/l; bilirrubina total, 2 mg/dl con fracción directa de 1,3 mg/dl; leucocitos, 19.400 (el 85,6% neutrófilos). En la radiografía simple, se detecta elevación de hemidiafragma derecho; se realiza tomografía computarizada (TC) toracoabdominal, y se observa un pequeño derrame pleural derecho y condensación en el segmento basal posterior del lóbulo inferior derecho, así como dos masas de aspecto poliquístico con captación de contraste tanto de la pared externa como de los septos internos, de 13 y 7,7 cm, que ocupan la práctica totalidad de los segmentos superiores del lóbulo derecho (VII y VIII) y parte de V y VI y un par de adenopatías significativas en hilio hepático. La imagen es altamente compatible con proceso neoplásico, si bien no se puede descartar otras enfermedades, como quiste hidatídico o absceso (fig. 1). Se pauta antibioterapia con imipenem y metronidazol, que no consigue revertir el mal estado general del enfermo y la persistencia de leucocitosis. Se decide practicar otra TC toracoabdominal, que aporta un derrame pleural derecho importante que produce desplazamiento mediastínico contralateral, con encapsulamiento paramediastínico anterior y paracardíaco, y se colecciona en receso pleural posterior derecho, desplazando al esófago contralateralmente, con condensación secundaria a atelectasia por compresión del lóbulo superior derecho. Se mantienen las tumoraciones hepáticas observadas previamente. Dada la disnea sintomática del enfermo, se procede a toracocentesis diagnóstica de 1.200 ml de líquido turbio amarillento, cuyo análisis final demostró un trasudado gramnegativo. Se decide intervención quirúrgica, dado que el cuadro no se ha resuelto y que son múltiples los diagnósticos diferenciales, con consulta previa al servicio de hematolo-