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J Santoyo,
B Sanchez, M de la Mata,
J L Fernández-Aguilar,
P Lopez-Ciller,
J M Pascasio,
M A Suarez,
M A Gomez,
F Nogueras,
K Muffak,
N Cuende,
M Alonso
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ABSTRACT: To evaluate the results of liver transplantation (OLT) performed for hepatocellular carcinoma (HCC) among a multicenter cohort of patients with predefined common inclusion and priorization criteria.
Over a 5-year period (January 2002-December 2006), 199 HCC patients underwent OLT in four centers in Andalusia. The morphological (Milan) inclusion criteria were priorized in two consecutive periods, according to the Model for End-stage Liver Disease score: group I, 53 patients (HCC < 2 cm = 24 points; > or = 2 cm or multinodular = 29 points) and group II, 146 cases (HCC < 3 cm without priorization; HCC > or = 3 cm or multinodular = 18 points).
Among the 199 HCCs, 186 (93.5%) subjects were transplanted and 13 (6.5%) were excluded. There were 18 cases (9.7%) where the diagnosis was incidental and 168 were known HCC cases; 144 (85.7%) complied with the Milan criteria (Milan+); 24 (14.3%) exceeded there criteria (Milan-). According to preoperative imaging, the number of nodules and tumor mean sizes among the excluded-Milan+ and Milan- groups-were 1.8/5.3 cm, 1.4/3.5 cm, and 2.3/6.7 cm, respectively (P < .001). Percutaneous treatment during listing was delivered to 55% of the excluded cases: 49% of Milan+ and 96% of Milan-. The median time on the list was 88 days for known HCC (53 days for group I, and 97 days for group II), and 172 days for the incidental HCCs. Staging (pTNM) was correct in 64% of cases: 23% were understaged and 13% were overstaged. Overall mortality within the first 90 days was 9%, and transplant patient survival at 5 years was 61%. No differences were observed in survival rates between both study periods, although there were differences between the Milan+ (65%) and Milan- (23%) groups (P < .04). In addition, the difference in the recurrence rates was also significant between the Milan+ (7%), Milan- (24%), and the incidental (25%) groups (P < .02).
A common priorization policy of HCC for OLT based on morphological criteria results in a low exclusion rate on the waiting lists (6.5%). The Milan criteria are still a good cutoff to stratify the risk of recurrence, despite preoperative tumor staging being correct in only two-thirds of cases.
Transplantation Proceedings 04/2009; 41(3):1009-11. · 1.00 Impact Factor
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ABSTRACT: 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.
Transplantation Proceedings 12/2008; 40(9):2990-3. · 1.00 Impact Factor
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ABSTRACT: 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.
Transplantation Proceedings 12/2008; 40(9):2952-4. · 1.00 Impact Factor
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A Rodríguez-Ariza,
A Monrobel,
E Martínez-Galisteo,
C Alicia Padilla,
J A Bárcena,
E Fraga,
G Costán,
P Barrera,
A Poyato,
J L Montero,
P López-Cillero,
J Muntané, M de la Mata
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ABSTRACT: the postoperative evolution of patients submitted to orthotopic liver transplant (OLT) is frequently associated with the appearance of different types of complications such as renal failure, graft rejection, infections, and neurological disorders. These complications are the most significant causes of early morbidity and mortality in patients undergoing OLT. The purpose of the present study was the identification of factors related to the different postoperative complications after OLT. Experimental design: a prospective study was carried out.
seventy-eight variables were analyzed in 32 consecutive patients undergoing OLT. The factors independently associated with the appearance of postoperative complications were identified using a stepwise logistic regression analysis.
the multivariate analysis showed that malondialdehyde and creatinine pretransplant serum levels were associated with the development of renal dysfunction. The pretransplant levels of haemoglobin and the units of platelets administered during surgery were prognostic factors of infections. Acute graft rejection was predicted by ?-glutamyl transpeptidase and total bilirubin serum levels. The pretransplant sodium and glutaredoxin levels in serum were associated with neurological complications.
we propose these markers for the identification of high-risk patients allowing an early surveillance and/or treatment to improve morbidity and survival in patients submitted to OLT.
Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 04/2008; 100(3):129-38. · 1.55 Impact Factor
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ABSTRACT: The use of marginal liver donors can affect the outcomes of liver transplantation in patients with hepatitis C virus (HCV) infection. There are no firm conclusions about which donor criteria are important for allocation of high-risk grafts to recipients with HCV cirrhosis. We performed 120 consecutive liver transplantations for HCV infection between 1995 and 2005. Marginal donor criteria were considered to be: age >70 years, macrovesicular steatosis >30%, moderate-to-severe liver preservation injury, high inotropic drug dose (dopamine >15 microg/kg/min; epinephrine, norepinephrine, or dobutamine at any doses), peak serum sodium >155 mEq/L, any hypotensive episode <60 mm Hg and >1 hour, cold ischemia time >12 hours, ICU hospitalization >4 days, bilirubin >2 mg/dL, AST and/or ALT >200 UI/dL. Graft survival with donors showing these marginal criteria was compared with optimal donors using Kaplan-Meier analysis and the log-rank test. Independent predictors of survival were computed with the Cox proportional hazards model. Fifty-six grafts (46%) were lost during follow-up irrespective of the Model for End-Stage Liver Disease (MELD) scores of the recipients in each category. Upon univariate analysis, grafts with moderate-to-severe steatosis (P = .012), those with severe liver preservation injury (P = .007) and prolonged cold ischemia time (P = .0001) showed a dismal prognosis at 1, 3, and 5 years. Upon multivariate analysis, fat content (P = .0076; OR = 4.2) and cold ischemia time >12 hours (P = .034; OR = 7.001) were independent predictors of graft survival. Among HCV recipients, marginal liver donors worked similar to those from "good" donors, except for those with fatty livers >30%, especially when combined with a prolonged cold ischemia time.
Transplantation Proceedings 09/2007; 39(7):2297-9. · 1.00 Impact Factor
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Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 08/2007; 99(7):405-10. · 1.55 Impact Factor
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ABSTRACT: The benefit of the triple therapy (interferon + amantadine + ribavirim) is still unknown. The efficacy of induction doses of interferon-alpha-2a monotherapy or in combination with ribavirin and/or amantadine was evaluated in interferon non-responders with chronic hepatitis C. A total of 378 patients were randomized. All the groups received the same doses and duration of interferon-alpha-2a: (i) interferon 9 MUI/day for 4 weeks and then 3 MUI/3 t.i.w. for 44 weeks (n = 53); (ii) interferon in combination with amantadine 100 mg twice daily for 48 weeks (n = 111); (iii) interferon in combination with ribavirin 1000-1200 mg (n = 106); (iv) interferon in combination with amantadine and ribavirin (n = 108). Baseline parameters were similar in the four groups. Sustained virological and biochemical responses were 13%, 6%, 18% and 22% respectively. No significant differences were found between double ribavirin arm vs triple therapy, but the difference was significant between interferon-amantadine (P = 0.008) and triple therapy (P = 0.0005). Hence, the induction doses of interferon in combination with ribavirin or ribavirin plus amantadine showed encouraging results in patients with chronic hepatitis C who were resistant to interferon. However, triple therapy is not superior to double.
Journal of Viral Hepatitis 03/2007; 14(2):89-95. · 4.09 Impact Factor
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J L Montero,
J C Pozo,
P Barrera,
E Fraga,
G Costán,
J L Domínguez,
J Muntané,
A Rodriguez-Ariza,
M Pleguezuelo,
S Rufián,
P López-Cillero, M de la Mata
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ABSTRACT: Pruritus is a common complication of cholestatic liver diseases or liver graft dysfunction. Current medical therapies lack efficacy. The molecular adsorbent recirculating system (MARS) represents an interesting therapeutic option. Our objective was to report our experience in the management of four patients with intractable pruritus with MARS.
The MARS treatment cycle included three consecutive treatments, each of 8 hours duration. The four patients with intractable pruritus who were treated had primary biliary cirrhosis/autoimmune hepatitis overlap syndrome (n = 1), ductopenic allograft rejection (n = 2), or posttransplant cholestatic HCV recurrence (n = 1). Intensity of pruritus was documented 24 hours before as well as 24 hours, 7 and 30 days after MARS therapy, and at the end of follow-up. We measured complete blood cell counts, glucose, BUN, creatinine, sodium, potassium, AST, ALT, GGT, alkaline phosphatase, bilirubin, prothrombin activity, and activated partial thromboplastin time.
MARS therapy was well tolerated. Patient 1 experienced temporal relief of pruritus, but needed another MARS cycle because of relapse. Patient 2 experienced partial and temporary relief of pruritus, was listed for retransplantation, and received a liver graft 2 months later. Patient 3 showed a dramatic reduction in the degree of pruritus with MARS. Pruritus in patient 4 decreased promptly with MARS therapy and conversion of immunosuppression to tacrolimus, thereby avoiding retransplantation.
MARS therapy is a promising, safe therapeutic option to treat refractory pruritus caused by cholestatic liver disorders.
Transplantation Proceedings 11/2006; 38(8):2511-3. · 1.00 Impact Factor
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E Bernal,
J L Montero,
M Delgado,
E Fraga,
G Costán,
P Barrera,
P López-Vallejos,
G Solórzano,
S Rufián,
J Briceño,
J Padillo,
P López-Cillero,
T Marchal,
J Muntané, M de la Mata
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ABSTRACT: Orthotopic liver transplantation (OLT) is the best treatment for nonresectable hepatocellular carcinoma (HCC), but tumor recurrence reduces long-term and medium-term survival. The effectiveness of adjuvant chemotherapy to prevent tumor recurrence has not been fully established. METHODS: Three hundred eighty-seven consecutive patients, including 43 with HCC superimposed on liver cirrhosis, underwent OLT. Twelve patients with one or more prognostic criteria for HCC recurrence were entered into a prospective prophylaxis protocol with monthly cycles of cisplatin (60 mg/m(2)) and adriamycin (30 mg/m(2)), beginning the fourth week post-OLT for a maximum of seven sessions. RESULTS: The 5-year survival of the non-HCC patients was 65.7% and that of the HCC patients was 60.46% (P = NS). Chemotherapy was reasonably well tolerated, but the 9 patients with hepatitis C- or B-associated cirrhosis showed viral and histological recurrence of the primary disease. A high proportion of patients (7 of 12) developed tumor recurrence during the first year after OLT. Six of these patients died, all but one due to HCC relapse. Five patients remain healthy and tumor free at 58 to 130 months. Post-OLT adjuvant chemotherapy does not avoid tumor recurrence and its fatal consequences but may contribute to prolonged tumor-free survival among a significant proportion of patients with high-risk HCC. However, the uncertain implications on viral recurrence and the lack of control groups do not allow post-OLT chemotherapy to be recommended outside controlled clinical trials, which are clearly warranted.
Transplantation Proceedings 11/2006; 38(8):2495-8. · 1.00 Impact Factor
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R Bárcena,
S Del Campo,
G Moraleda,
T Casanovas,
M Prieto,
M Buti,
J M Moreno,
V Cuervas,
E Fraga, M De la Mata, [......],
C Loinaz,
C Barrios,
M L G Dieguez,
A Mas,
J M Sousa,
J I Herrero,
R Muñoz,
J F Avilés,
A Gonzalez,
M Rueda
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ABSTRACT: Hepatitis B virus (HBV) recurrence and de novo HBV infection are frequent events in liver transplantation recipients. Treatment with lamivudine is initially efficient in both infections but the incidence of lamivudine-resistant HBV emergence increases over time. Adefovir appears to be promising in post-liver transplantation patients with recurrent HBV infection and lamivudine-resistant HBV. This study analyzed adefovir treatment in 42 post-liver transplantation patients who developed recurrent HBV or de novo HBV infection with lamivudine-resistant HBV (54.8% HCV-coinfected). Patients received 10 mg of oral adefovir once daily for a mean period of time of 21.5 months (range from 12 to 31 months). In 62.9% of patients, ALT levels decreased significantly. Serum HBV-DNA was undetectable in 64% of the cases. Twenty percent of patients lost HBeAg marker and 13.3% of them developed anti-HBe. In 9.5% of recipients, HBsAg became negative. There was no significant change in serum creatinine levels. In only one patient was worsening of the renal function detected, making dose adjustment necessary. No other side effects were reported. Our results confirm the efficacy and safety of adefovir treatment in post-liver transplantation patients with lamivudine-resistant HBV, neither were adefovir-resistant mutations identified in patients after 21 months of therapy, nor were there adverse events, especially renal toxicity.
Transplantation Proceedings 12/2005; 37(9):3960-2. · 1.00 Impact Factor
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Gastroenterología y Hepatología 11/2004; 27 Suppl 4:62-5. · 0.73 Impact Factor
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Gastroenterología y Hepatología 03/2004; 27 Suppl 1:52-6. · 0.73 Impact Factor
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ABSTRACT: A cohort of 65 liver transplant recipients was prospectively monitored with qualitative polymerase chain reaction (PCR) in plasma. The first 25 patients did not receive prophylaxis. From a consecutive group of 40 recipients, 11 high-risk patients donor CMV-seropositive/receptor CMV-seronegative (D+/R-), persistent CMV replication) received pre-emptive oral ganciclovir (1000 mg three times daily), when a marker of risk was identified, until day 90. The overall incidence of cytomegalovirus (CMV) disease at six months was 20% (five of 25 patients) in the non-prophylaxis group and 2.5% (one of 40 patients) in the group treated with pre-emptive oral ganciclovir (relative risk, 0.11; 95% confidence interval; 0.01-0.96; P = 0.04). The PCR sensitivity for detecting CMV disease was 80%, the specificity was 90%, and the positive and negative predictive values were 66% and 95%, respectively. Adverse events, graft rejection and survival were similar between groups. We conclude that pre-emptive oral ganciclovir in high-risk patients can reduce the risk of CMV disease.
Clinical Microbiology and Infection 01/2003; 8(12):773-80. · 4.54 Impact Factor
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Transplantation Proceedings 09/2002; 34(5):1511-3. · 1.00 Impact Factor
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ABSTRACT: The aim of the present study was to analyze the characteristics of bacteremia occurring in liver-transplant patients in Andalusia, Spain, during the 1990s. At the three participating hospitals, 405 liver transplantations were performed during the study period, and 119 bacteremic episodes were observed following 91 of them (22.4%, 29.4 episodes/100 liver transplants). Gram-positive organisms were the predominant bacteria isolated in cases of early-onset bacteremia (70.7%, P=0.04). The most common sources of bacteremia were the abdomen (33.6%) and intravascular catheters (22.7%), but frequently the source of bacteremia was unknown (31.9%). Mortality at 30 days was 21%. Isolation of Staphylococcus aureus was the only independent risk factor for mortality (relative risk, 3.13; 95% confidence interval, 1.3-7.5; P=0.01). These results indicate that control measures are required in order to reduce the incidence of gram-positive bacteremia and catheter-related infection in this patient population. The observed etiology must be considered when empirical antimicrobial therapy is indicated while awaiting blood-culture results.
European Journal of Clinical Microbiology 06/2002; 21(5):385-8. · 2.86 Impact Factor
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A Quintero,
C A Pedraza,
E Siendones,
A M Kamal ElSaid,
A Colell,
C García-Ruiz,
J L Montero, M De la Mata,
J C Fernández-Checa,
G Miño,
J Muntané
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ABSTRACT: D-galactosamine (D-GalN) toxicity is a useful experimental model of liver failure in human. It has been previously observed that PGE1 treatment reduced necrosis and apoptosis induced by D-GalN in rats. Primary cultured rat hepatocytes were used to evaluate if intracellular oxidative stress was involved during the induction of apoptosis and necrosis by D-GalN (0-40mM). Also, the present study investigated if PGE1 (1 microM) was equally potent reducing both types of cell death. The presence of hypodiploid cells, DNA fragmentation and caspase-3 activation were used as a marker of hepatocyte apoptosis. Necrosis was measured by lactate dehydrogenase (LDH) release. Oxidative stress was evaluated by the intracellular production of hydrogen peroxide (H2O2), the disturbances on the mitochondrial transmembrane potential (MTP), thiobarbituric-reacting substances (TBARS) release and the GSH/GSSG ratio. Data showed that intermediate range of D-GalN concentrations (2.5-10mM) induced apoptosis in association with a moderate oxidative stress. High D-GalN concentration (40 mM) induced a reduction of all parameters associated with apoptosis and enhanced all those related to necrosis and intracellular oxidative stress, including a reduction of GSH/GSSG ratio and MTP in comparison with D-GalN (2.5-10 mM)-treated cells. Although PGE1 reduced apoptosis induced by D-GalN, it was not able to reduce the oxidative stress and cell necrosis induced by the hepatotoxin in spite to its ability to abolish the GSH depletion.
Free Radical Research 04/2002; 36(3):345-55. · 2.88 Impact Factor
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ABSTRACT: Bioartificial liver support has been increasingly the focus of both basic and clinical research in an attempt to replicate the multiplicity of normal liver function. The concept is attractive because, if it is effective, patients with acute liver failure may be supported until native liver regeneration occurs or, by optimizing their condition, until liver transplantation is possible. Current bioartificial liver support systems utilize primary porcine hepatocytes or transformed human hepatocytes, which are housed within a bioreactor, through which the patient's blood or plasma is pumped in an extracorporeal circuit. The optimal source for the hepatocytes is an area of debate; however, a genetically engineered cell line may provide optimal function. Novel three-dimensional matrices that anchor the hepatocytes are being designed to mimic architectural features of the normal liver. Large multicentre, randomized, controlled trials are ongoing following several pilot studies. Serious side effects such as hemodynamic instability and immune reactions have been infrequent. Much controversy, however, surrounds the issue of possible transmission of pig endogenous retrovirus to humans, and current trials are being carefully monitored. Bioartificial liver support is a promising technology, and the results of current and planned studies are awaited with great interest.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie 06/2001; 15(5):313-8. · 1.21 Impact Factor
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ABSTRACT: The aim of the present study was to analyze the efficacy and tolerance of interferon (IFN) therapy in hemodialysis (HD) patients with chronic hepatitis C virus (HCV) infection. Specifically, we assessed whether the "normalization" of serum ALT levels was associated with the disappearance of the HCV-RNA.
Thirteen hemodialysis patients with chronic hepatitis C were treated for one year with 3 MU of alpha-IFN. The primary end point was a sustained virological response defined as the absence of HCV-RNA in the last follow-up; the secondary end points were normalization of the serum ALT levels and histological improvement. ALT was considered "normal" below 27 IU/l.
Ten patients completed the treatment, which was discontinued in the other 3 (23%). By the end of the treatment a virological response was observed in 8 of the 10 patients (80%) who completed the one-year IFN therapy. Biochemical response was associated with a virological response in 8 of the 9 patients in whom ALT levels became normal. Three patients had a biochemical and virological relapse in the follow-up. Two of them received a further year of IFN therapy, which resulted in a sustained biochemical and virological response. In all patients who underwent a liver biopsy (n = 5), the inflammation score improved. After a median follow-up of 5 years (range 2 - 7), a sustained response was observed in 6 (46%) of the 13 patients enrolled. Two patients with a sustained response received a kidney transplant and after more than 6 years still maintain a biochemical and virological response. Side effects included flu-like syndrome (n = 8), hemoglobin decrease (n = 8), thrombocytopenia (n = 3), depression (n = 1) and seizures (n = 1).
IFN treatment over a one-year period produces a high rate of long-term virological response in HD patients, associated to a biochemical response in all cases.
Clinical nephrology 03/2001; 55(3):220-6. · 1.17 Impact Factor
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Journal of Hepatology 02/2001; 34(1):173. · 9.26 Impact Factor
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Gastroenterología y Hepatología 02/2001; 24(1):37-46. · 0.73 Impact Factor
