Tenofovir/entecavir monotherapy after hepatitis B immunoglobulin withdrawal is safe and effective in the prevention of hepatitis B in liver transplant recipients.

BACKGROUND AND AIMS: Combination of hepatitis B immunoglobulin (HBIG) and a nucleos(t)ide analog (NA) is considered the standard of care for prophylaxis of hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, use of lifelong HBIG has significant limitations. We evaluated the efficacy and safety of entecavir (ETV) or tenofovir disoproxil fumarate (TDF) after withdrawal of HBIG in patients who had been under HBIG-regimen prophylaxis post LT. METHODS: Patients at low risk of recurrence were eligible for HBIG discontinuation (fulminant HBV hepatitis, co-infection with hepatitis D virus, and hepatitis B e antigen-negative cirrhotic patients with HBV DNA levels <300 copies/mL). All patients had received HBIG, with or without NA, for at least 12 months after LT. After HBIG discontinuation, they continued with ETV or TDF monotherapy. Patients were followed up with HBV serum markers and evaluation of renal function. RESULTS: Between September 2011 and June 2014, 58 liver transplant recipients were converted to TDF (31, 53%) or ETV (27, 47%). Mean follow-up after conversion was 28 ± 5 months (range 13-36 months). Five patients (8.6%) developed detectable hepatitis B surface antigen at 7, 9, 13, 15, and 22 months after HBIG discontinuation. However, in every case seroconversion was transitory, serum HBV DNA was undetectable, with no clinical manifestations of HBV recurrence. No adverse effects were observed or dose reductions required associated with ETV or TDF. CONCLUSIONS: Maintenance therapy with newer NAs, after discontinuation of HBIG prophylaxis, was safe and effective, with a low rate of serological recurrence and no evident clinical, biochemical, or virological consequences.

Influence of antiviral therapy in the long-term outcome of recurrent hepatitis C virus infection following liver transplantation.

INTRODUCTION: Severity of recurrent hepatitis C virus (HCV) infection in liver transplant recipients (LTR) is variable and the influence of different factors, including the administration of antiviral therapy in the long-term outcome is controversial. METHODS: We analyzed the outcome of a cohort of HCV-infected LTR who were transplanted in our institution. Patients were divided into 2 groups (severe and non-severe HCV disease) depending on the presence of a fibrosis score of F ≥ 2 in the Scheuer index and/or fibrosing cholestasic hepatitis (FCH) in a graft biopsy. Risk factors were studied using logistic regression analysis. Survival of patients was estimated using Kaplan-Meier plots. A total of 146 patients were followed for a mean of 58 months. RESULTS: Fifty-six (34%) patients developed severe HCV disease and showed shorter survival (P < 0.024). Donor age (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.02-1.06) and pre-transplant viral load (VL) >10(6) UI/mL (OR: 3.5; 95% CI: 1.42-10.61) were the only factors associated with severe HCV infection. Over-immunosuppression (OR: 2.3; 95% CI: 1.2-4.41) was specifically associated with the development of FCH. Overall, patient survival in recipients who received a full course of anti-HCV therapy was higher than in patients who did not complete antiviral therapy (P = 0.004) or received no treatment (P = 0.007). Patients with non-severe HCV infection have a higher probability of receiving a full course of antiviral therapy (P = 0.033). CONCLUSION: In conclusion, donor age, pre-transplant VL, and over-immunosuppression were associated with the long-term development of severe HCV recurrence in liver grafts. Administration of a full course of antiviral therapy was associated with better survival.

Pregnancy and orthotopic liver transplantation.

BACKGROUND: Sexual and reproductive abnormalities affect up to 50% patients with terminal liver failure. However, these functions recover quickly after orthotopic liver transplantation (OLT). Thus, 80%-90% of OLT women of childbearing age recover menstruation within a few months after transplantation. The aim of our study was to analyze the impact of pregnancy among liver transplant recipients at our center, as well as to analyze the effects of immunosuppression on the fetus. METHODS: From April 1986 to April 2011, we performed 1500 OLT in 1341 recipients. Among these recipients, 18 patients (1.2%) become pregnant during the follow-up. RESULTS: The most frequent causes of terminal liver failure were as follows: chronic parenchymal disease (n = 9; 50%), cholestatic disease (n = 3; 16.6%), acute liver failure (n = 5; 27.7%), and metabolic disease (n = 1; 5.5%) The average recipient age at the beginning of pregnancy was 21.2 (±7.3) years. Sixteen patients (88%) became pregnant beyond a year after OLT. The 30 pregnancies in our study resulted in the following: newborns alive (NBA; n = 20; 66.6%) abortions (n = 8; 26.6%) or fetal deaths (n = 2; 6%). The most common immunosuppressant used during pregnancy was tacrolimus (75%) followed by cyclosporine (25%). There were no maternal deaths during pregnancy or the postpartum period. DISCUSSION: We did not observe significant differences between immunosuppression type and maternal complications, pregnancy duration, and childbirth type. Although pregnancy is potential risk, the literature and our results suggest that at a year or more after OLT it usually is safe and successful.

Everolimus monotherapy or combined therapy in liver transplantation: indications and results.

INTRODUCTION: Everolimus is a potent immunosuppressant with several advantages over calcineurin inhibitors, such as good tolerance, preventive effects on cardiovascular morbidity, and mortality and cancer prevention as it inhibits cell proliferation. PATIENTS AND METHODS: Between April 1986 and December 2010, we performed 1500 liver transplants (OLT) in 1341 recipients, including 57 patients who were prescribed everolimus 24 (42.1%) as monotherapy and 33 (57.9%) as treatments combined with other immunosuppressants. We performed a retrospective analysis of our experience with conversion to everolimus in OLT recipients. RESULTS: The 43 men and 14 women had a mean overall age at transplantation of 59.1 ± 10 years. The most frequent indication for OLT was hepatocellular carcinoma (HCC; 53.8%). Everolimus was introduced to prevent HCC recurrence (53%), development of de novo tumors (33%), address renal dysfunction (7%), or overcome side effects of other immunosuppressants (7%). We observed a significant improvement in renal function using the estimated glomerular filtration rate (Crockcroft-Gault formula) from 68.5 mL/min before to 74.5 mL/min after switching to everolimus. The 72% of recipients who developed ≥1 adverse event, most frequently showed hyperlipidemia (34.4%). CONCLUSION: Both monotherapy and combined everolimus regimens were well-tolerated immunosuppressive regimens in liver transplant recipients with recurrent or de novo malignancies. Everolimus improved renal function. The most common side effects were hyperlipidemia, edema, and mouth ulcerations, which were well controlled with anti-lipidemic agents or decreased everolimus dosages.

Liver transplantation from anti-hepatitis C virus-positive donors: our experience.

BACKGROUND: Hepatitis C (HCV) is among the most common causes of end-stage liver disease worldwide. The donor shortage leads us to consider alternative organ sources such as HCV-positive donors. The outcomes of these transplants must be evaluated thoroughly since there is universal recurrence of disease among HCV-positive liver transplant recipients. METHODS: From January 2005 to April 2011, we performed 143 liver transplants (OLT) to treat end-stage liver disease secondary to HCV infection. Thirteen patients (9,1%) received livers from HCV-positive donors. A control group consisted of 130 HCV-positive patients who underwent OLT during the same period with organs from HCV-negative donors. Donor HCV status was assessed by 2 tests: HCV antibodies and viral load. Not only recipient and graft survivals were analyzed, but also frequency, timing and severity of hepatitis recurrence. RESULTS: Among 143 transplants performed in HCV-positive recipients during a 6-year period from January 1, 2005, to April 30, 2011, 9.1% of patients received an organ from an anti-HCV-positive donor, 72.7% of whom showed a negative viral load. The vast majority (80%) of our patients suffered hepatitis during their follow-up, 22.4% of which were severe cases. CONCLUSIONS: No significant difference in patient or graft survival was observed between the 2 groups. A high percentage of grafts with initial positive serology for HCV showed no viral replication. Grafts from HCV-positive donors can be considered to be a safe, effective source for liver donation.

Split liver transplantation: where? when? how?

Donor scarcity is among the greatest concerns in the transplantation community. Dividing a liver graft theoretically offers a double benefit for candidates on the waiting list. Split liver transplantation entails a higher logistic and technical complexity that is extensively compensated, not only with an increase in the accessibility for child and adult candidates on the liver transplant waiting list, but also acceptable survival results.

Liver retransplantation in HIV-infected patients: a prospective cohort study.

Information regarding liver retransplantation in HIV-infected patients is scant. Data from 14 HIV-infected patients retransplanted between 2002 and 2011 in Spain (6% retransplantation rate) were analyzed and compared with those from 157 matched HIV-negative retransplanted patients. In HIV-infected patients, early (≤30 days) retransplantation was more frequently indicated (57% vs. 29%; p = 0.057), and retransplantation for HCV recurrence was less frequently indicated (7% vs. 37%; p = 0.036). Survival probability after retransplantation in HIV-positive patients was lower than in HIV-negative patients, 42% versus 64% at 3 years, although not significantly (p = 0.160). Among HIV-infected patients, those with undetectable HCV RNA at retransplantation and those with late (>30 days) retransplantation showed better 3-year survival probability (80% and 67%, respectively), similar to that in their respective HIV-negative counterparts (72% and 70%). In HIV-infected and HIV-negative patients, 3-year survival probability in those with positive HCV RNA at retransplantation was 22% versus 65% (p = 0.008); in those with early retransplantation, 3-year survival probability was 25% versus 56% (p = 0.282). HIV infection was controlled with antiretroviral therapy after retransplantation. In conclusion, HIV-infected patients taken as a whole have unsatisfactory survival after liver retransplantation, although patients with undetectable HCV RNA at retransplantation or undergoing late retransplantation show a more favorable outcome.

Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study.

Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI, 2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV-infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5-year prognosis (69%[95% CI, 54-80]) to that of HCV-monoinfected recipients. In conclusion, 5-year survival in HCV/HIV-coinfected liver recipients was lower than in HCV-monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.

In vitro evaluation of new possible cell engraftment enhancers for cell transplantation.

Orthotopic liver transplantation (OLT) is the best treatment to restore liver function in liver failure. The low availability of organs has focused interest on the use of cell transplantation to restore liver function. However, this technique is limited because cells can not bind to liver parenchyma and die soon after perfusion. Pretransplant treatment with engraftment enhancers (EE) to increase vascular permeability may increase cell attachment. Using an endothelial cell culture to measure the loss of intercellular endothelial adhesion as a screening test, we evaluated the capacity of 15 monoclonal antibodies against adhesion molecules expressed on endothelial cells to act as EE showing that 3 antibodies (anti-CD54, efalizumab, and abciximab) act as EE by producing disruptions in the cell layer.

Evaluation of Anti-HBs serum levels and pharmacokinetic profile after intravenous administration of Niuliva, a new hepatitis B immunoglobulin, following liver transplantation.

PURPOSE: We assessed whether trough anti-hepatitis B surface antigen (HBs) serum levels considered to be protective (>100 IU/L) were maintained in liver transplanted patients after 6 months of uninterrupted treatment with Niuliva, a new intravenous HBIg. METHODS: Twenty patients, aged 18-70 years, who had undergone liver transplantation due to HBV-related liver disease at least 1 year before inclusion were enrolled in a prospective, open-label, uncontrolled, multicenter clinical study. A fixed monthly dose of 5,000 IU of study medication was administered intravenously for 6 months. RESULTS: After the second infusion, all mean values of anti-HBs and 95% CIs were above the limit of 100 IU/L considered to be protective. The percentages of success ranged between 95% (95% CI 75.1%-99.9%) and 100% (95% CI 86.1%-100%). Mean values and 95% CI of in vivo recovery of anti-HBs at 15-30 minutes after each infusion showed overlaps between all intervals, which indicated that significant differences were not present in the recovery of post infusion anti-HBs in vivo. There were no recurrences of HBV infection during the study. There were no seroconversions in patients previously negative to hepatitis C virus or HIV. No serious adverse events related to the study medication were observed. CONCLUSIONS: Serum levels of anti-HBs after using Niuliva in patients who had undergone liver transplantation were protective in 95%-100% of cases after the study period. This new HBIg showed the expected pharmacokinetic profile and was well tolerated and safe.

Short- and long-term overall results of liver retransplantation: "Doce de Octubre" hospital experience.

INTRODUCTION: The liver retransplantation rate in Spain is about 6%. The main causes are primary nonfunction, vascular complications, chronic rejection, and recurrent liver disease. The results of this procedure are worse than those of first transplantations. PATIENTS AND METHODS: This retrospective study evaluated our experience with 54 retransplantations performed between January 1992 and December 2006, which were 5.6% of the 960 orthotopic liver transplantations (OLT) during this period. RESULTS: In this study, 34.7% of the retransplantations were performed between 4 and 30 days after the first transplantation; another 34.7% were within 1 year. Also, 48.9% of the retransplantations were performed in urgent situations. The main causes for retransplantation during the first month were primary hepatic failure (n = 14) and vascular complications (n = 4). After the first month the main causes were chronic rejection (n = 9), recurrence of hepatic disease (n = 3), and biliary complications (n = 4). Postoperative mortality was 23.9% and morbidity was 76.3%. However, 21.2% of the patients needed a third transplant. The overall rate of patient survival was 60.4% (n = 32) and of graft survival was 56.6% (n = 30). The 5-year actuarial graft survival rate was 65.4% with a mean survival time of 89.84 +/- 8.72 months; the 5-year patient survival rate was 64% with a mean survival time of 114.7 +/- 12.53 months. Worse survival was observed in chronic rejection and in retransplantations performed between 31 and 360 days. CONCLUSIONS: Liver retransplantation presents greater surgical complexity than the first transplantation, but is a good option for patients with failure of the first graft with a 5-year patient and graft survival rate greater than 65%.

An in vitro model of cell transplantation for evaluation of cell engraftment enhancers.

The limited availability of organs for liver transplantation has focused interest on the use of cell transplants to restore hepatic function. Advances have been made in rodent models, but efficacy is limited in humans due to low engraftment efficiency. In rodents, pretransplantation treatment of the liver with engraftment enhancers (EE) shows that repopulation is feasible, although the toxicity of the substances impedes their application in humans. Evaluation of low-toxicity engraftment enhancers for human use requires testing in animal models, a time-consuming, expensive process that also raises ethical issues. To reduce animal use in the preliminary evaluation of a new EE, we designed an easily quantitated in vitro method that mimics an intraportal cell transplant. It is based on EE-mediated disruption of intercellular adhesion in confluent endothelial cell cultures.

Starting a new program of split liver transplantation after a low learning curve: a reality in centers with large experience in liver surgery and whole liver transplantation.

BACKGROUND/AIMS: Split liver transplantation (SLT) is nowadays, considered an adequate surgical solution to expand the grafts from the existing pool of cadaveric donors. METHODOLOGY: A total of 897 liver transplantations were performed between 1986 and 2002; 20 were SLTs (2.3%). A 30% were children. RESULTS: Mean follow up of 15.15 months +/- 13.85. Median age was 42.27 +/- 25.65 yrs. Median recipient weight was 52.29 +/- 20.87 Kg. Mean donor weight was 76.1 +/- 13.11. The majority was "in situ" SLT (65%). There was no primary graft dysfunction. Two patients developed biliary complications (none in situ SLT). Early HAT occurred in 2 patients and delayed HAT in one. Four patients were retransplanted but none were performed because of primary graft dysfunction. Five patients died in the hospital. Fifteen patients (75%) survived the postoperative period and 3 patients died during follow-up. Mean patient survival time was 42 months (95% CI: 31-52). Actuarial patient survival was 93.3%, 84.4%, 84.4% at 6 months, 1 year and 3 years. Mean graft survival was 36 months (95% CI: 25-48). Actuarial graft survival was 87%, 72%, 72% at 6, 12, 36 months. Univariate analysis of risk factors for graft loss showed that the type of splitting technique (p=0.019), and the UNOS (1 and 2a) status of the recipient (p=0.001) were significantly associated with graft loss. CONCLUSIONS: In the context of large volume full cadaveric liver transplantation, split liver can provide adequate results (even after a short learning curve) mainly in elective cases and with the in situ technique.

Mycophenolate mofetil monotherapy in patients who underwent liver transplantation for hepatitis C cirrhosis.

INTRODUCTION: Mycophenolate mofetil (MMF) monotherapy has recently been proposed for liver transplant recipients with adverse events (nephrotoxicity, hypertension) related to calcineurin inhibitors. We analyzed the influence of MMF on the clinical course of recurrent hepatitis C. METHODS: Among 1038 patients who underwent liver transplantation (OLT) from April 1986 to October 2006, we analyzed 48 adult recipients (4.6%) whose diagnosis was hepatitis C virus (HCV) cirrhosis and who were converted from calcineurin inhibitors to MMF monotherapy. RESULTS: The 36 men and 12 women, had a mean age at OLT of 52.9 +/- 7.2 years; the time elapsed from OLT to the onset of MMF monotherapy was 72.5 +/- 47.6 months (range = 11-210). The mean follow-up after monotherapy was 19 +/- 16.1 months (range = 2-67). Indications for conversion were: chronic renal dysfunction with HCV in 45 patients; HCV recurrence in two; and hypertension plus HCV recurrence in one subject. When the indication was renal dysfunction (excluding three patients who underwent hemodialysis), the mean creatinine values decreased significantly from baseline to 6 months of monotherapy from 1.63 +/- 0.61 mg/dL to 1.51 +/- 0.78 mg/dL (P < .03). The creatinine clearance only improved significantly from the baseline value of 56.6 +/- 16.8 mL/min to the value at 3 months of monotherapy-63.6 +/- 18.4 mL/min (P < .001). At the last outpatient visit, creatinine and creatinine clearances had not changed significantly. The mean diastolic blood pressure did improve significantly at the end of the study. The mean glucose levels decreased but not significantly at the last outpatient visit. Liver function tests did not change significantly after conversion to MMF monotherapy. The acute rejection rate was 8.3%, and adverse events related to MMF monotherapy were present in 9 patients (18.7%). CONCLUSIONS: Conversion from calcineurin inhibitors to MMF monotherapy in patients who underwent OLT for HCV transiently improved renal function and hypertension. The acute rejection rate was low, and adverse events were usually well tolerated.

Influence of dialysis modality on complications and patient and graft survival after pancreas-kidney transplantation.

INTRODUCTION: We investigated whether hemodialysis or peritoneal dialysis prior to pancreas-kidney transplantation was a risk factor for the development of surgical complications, recipient mortality, or graft loss. PATIENTS AND METHODS: From March 1995 to December 2006, 90 patients with type 1 diabetes underwent pancreas transplantation. Dialysis before transplantation was provides to 81 patients. We compared outcomes of recipients classified as two groups: (A) hemodialysis (n = 49, 60.5%) versus (B) peritoneal dialysis (n = 32, 39.5%) groups. RESULTS: Donor and recipient characteristics were similar in both groups. Enteric drainage was more frequently used in the hemodialysis group and bladder drainage in the peritoneal dialysis group (P < .05). The rate of intra-abdominal infections was similar in both groups: 10 patients (20.4%) in the hemodialysis group and 9 patients (28.1%) in the peritoneal dialysis group (P = NS). The incidence of enteric or bladder leakage was slightly higher in the peritoneal dialysis group (5 cases, 15.6% vs 4 cases, 8.2% in the hemodialysis group; P = NS). The rate of reoperations was also slightly higher in the peritoneal dialysis group B (15 cases, 46.9% vs 14 cases, 28.6% in the hemodialysis group; P = .07). Pancreas transplantectomy was significantly greater in the peritoneal dialysis (9 cases; 28.1%) than the hemodialysis group (5 cases; 10.2%; P < .05). The actuarial 3-year patient survival was 95.9% in the hemodialysis group and 93.4% in the peritoneal dialysis group (P = NS); actuarial 3-year pancreas graft survival was 79.3% in the hemodialysis group and 68.3% in the peritoneal dialysis group (P = NS). CONCLUSIONS: We noted an insignificantly greater rate of reoperations but significantly higher incidence of pancreas transplantectomy in the peritoneal dialysis group; however, patient and pancreas graft survivals were similar in both study groups.

Pancreas preservation with the University of Wisconsin versus Celsior solutions.

INTRODUCTION: The use of Celsior solution for organ preservation has not been thoroughly studied in pancreas transplantation. The aim of this study was to compare University of Wisconsin and Celsior solutions for preservation of pancreas grafts. PATIENTS AND METHODS: From March 1995 to December 2005, 72 patients with type 1 diabetes underwent pancreas transplantation. There were 42 men and 30 women, with a mean age at transplantation of 38.1 +/- 7.5 years (range: 27 to 55 years), and a mean duration of diabetes of 22.5 +/- 6.6 years. Recipients were classified into two groups according to the preservation solution: (A) Celsior (n = 28, 38.9%) and (B) Wisconsin (n = 44, 61.1%). RESULTS: The donor and recipient characteristics were similar in both groups. There were five cases of venous thrombosis in the Wisconsin group and two in the Celsior group (P = NS). The venous drainage technique in the former group was portocaval in 19 patients and portoiliac in 25; in the Celsior group, portocaval in 23 patients and portoiliac in five (P = .001). Enteric drainage was used in 19 patients from the Celsior group and 17 patients from the Wisconsin group (P = .01). Actuarial 2-year graft survival was 74.6% in the Wisconsin group and 77.4% in the Celsior group (P = NS). CONCLUSIONS: No differences were observed in venous thrombosis between the two groups. The lower rate of venous thrombosis with the portocaval technique was related to the type of venous drainage rather than the type of preservation solution. Celsior solution may be considered as good as Wisconsin solution for pancreas transplantation.

Five-year follow-up of a trial comparing Tacrolimus and cyclosporine microemulsion in liver transplantation.

We evaluate 5-year results of a prospective randomized trial that compared cyclosporine microemulsion (CsA-me) and Tacrolimus (Tac) for primary immunosuppression. One hundred one adult patients undergoing liver transplantation were randomized to receive Tac (n = 50) or CsA-me (n = 51). The most frequent indication for the procedure was cirrhosis due to virus C followed by alcoholism. Survival rates at 1, 3, and 5 years were 86%, 75%, and 72%, respectively; there was no significant difference between CsA-me versus Tac arms. Acute rejection occurred in 30 cases (30%), independent of the type of primary immunosuppression. Serious adverse events were reported significantly more among patients under CsA-me (48 episodes) than under Tac (32 episodes). Nineteen patients were switched to the other calcineurin inhibitor. The switch was much more frequent from CsA-me to Tac (n = 15; 29.4%), mainly because of lack of efficacy (n = 10; 19.6%). There were no cases of chronic rejections in the Tac arm. Four patients were switched from Tac to CsA-me for side effects; only 1 remains alive, after treatment was changed from CsA-me to an antimetabolite. There were no statistical differences in renal dysfunction, diabetes, hypertension, neurologic disorders, new-onset malignancies, or infections. There were no differences in survival or rejection among the intention-to-treat groups. Serious adverse events, total patients with switch of calcineurin inhibitor, as well as switches due to lack of efficacy, were statistically more frequent under CsA-me. Tacrolimus seems to be a more appropriate drug to be used for primary immunosuppression in liver transplantation.

Comparative analysis of the results of orthotopic liver transplantation in patients with and without portal vein thrombosis.

INTRODUCTION: Portal vein thrombosis (PVT), which had been considered an absolute contraindication to orthotopic liver transplantation (OLT), is currently considered a risk factor that increases morbi-mortality. The objective of this study was to compare OLT outcomes in patients with vs without PVT. MATERIALS AND METHODS: Between April 1986 and December 2003, a sample of 83 patients with PVT was compared with another sample of 83 patients without PVT among 962 OLT performed in our department. RESULTS: Both groups were homogeneous in terms of epidemiological variables, surgical technique, immunosuppression, and donor-related variables. There were no differences with respect to graft function during the first week following surgery. Surgical time and anhepatic phase duration was longer in the PVT group, albeit the differences were not significant. PVT patients also required more transfusions; a strong statistical association was observed with respect to blood (P = .12) and plasma (P = .11) transfusions and statistically significant differences regarding platelet transfusions (P = .02). Time on mechanical ventilation and the length of stay in the ICU were longer but not significant among PVT patients. The only statistically significant difference was the incidence of portal rethrombosis (P = .02). With respect to mean and global patient and graft actuarial survivals after 1, 3, 5, and 10 years, we have observed no significant intergroup differences, although both patient (P = .48; NS) and graft (P = .96, NS) survivals were lower among PVT cases. CONCLUSIONS: PVT should not only cease to be considered a contraindication for OLT, but there were no significant differences between the outcomes despite this finding.

Modulation of hepatocyte growth factor plasma levels in relation to the dose of exogenous heparin administered: an experimental study in rats.

INTRODUCTION: Partial liver transplantation has been consolidated to be a valid treatment option. We sought to understand the factors that modulate and may be harnessed to accelerate hepatocyte regeneration. We sought to determine the impact of heparin on m-hepatocyte growth factor (HGF) plasma concentrations. MATERIALS AND METHODS: Sixteen rats were assigned to four groups of four animals each: group A, without heparin; group B, 600 IU/kg; group C, 1000 IU/kg, group D, 1400 IU/kg. Blood samples (0.5 mL) were obtained from each rat at baseline and at 30, 60, 120, and 240 minutes. After the samples were centrifuged to separate supernates from the cell phase they were stored at -20 degrees C in the m-HGF reagent and subsequently tested using enzyme-linked immunosorbent assay. Results were analyzed using SPSS 11.5 statistical software. RESULTS: Among the 16 rats, one died at 110 minutes, just prior to the last extraction. The remaining rats were sacrificed. Mean weight was: 466 +/- 64.24 g with no intergroup differences (P = .149). The comparative results (using Student t test) were: baseline A(1-4) versus A(1-4) 30 minutes: P < .05; baseline A(1-4) versus A(1-4) 60 minutes: P < .05; baseline A(1-4) versus A(1-4) 120 minutes: P = .10 (NS); baseline A(1-4) versus A(1-4) 240 minutes: P = .15 (NS). No significant differences were found among group B: baseline C(1-4) versus C(1-4) 30 minutes and 60 minutes: NS; baseline C(1-4) versus C(1-4) 120 minutes: P < .001; baseline C(1-4) versus C(1-4) 240 minutes: P < .10 (NS). Finally, the results in group D were: baseline D(1-4) versus D(1-4) 30 minutes: NS; baseline D(1-4) versus D(1-4) 60 minutes and 120 minutes: P < .05; baseline D(1-4) versus D(1-4) 240 minutes: P < .0005. When we compared group A to C and D, we detected differences (albeit not when compared to B) with P values = .01. Peak values were obtained at 120 and 240 minutes (225.21 pg/mL and 221.78 pg/mL) among groups C and D. CONCLUSION: Heparin has a positive effect to increase serum HGF concentrations among rats. The effect was dependent on the administered dose and the time elapsed.

Incidence and risk factors of development of lung tumors after liver transplantation.

INTRODUCTION: Lung tumors have been related to tobacco and alcohol. The incidence increases after orthotopic liver transplantation (OLT) especially when it is performed because of alcoholic cirrhosis. PATIENTS AND METHODS: We analyzed the incidence and risk factors for de novo lung tumors among 701 patients who underwent OLT between April 1986 and July 2004, after exclusion of pediatric recipients and adults who died within 2 months after OLT. RESULTS: The incidence of de novo lung tumors was 15 patients (2.1%), including 12 (4.3%) who underwent OLT for alcoholic cirrhosis and 3 (0.7%) for nonalcoholic diseases. There were 14 men and 1 woman of mean age at OLT of 50.8 +/- 9.6 years. Mean time from OLT to lung tumor was 83 +/- 43 months (range, 10-184 months). Thirteen patients (86.6%) were heavy smokers before OLT and 8 (61.5%) continued after OLT; 12 patients (80%) were heavy drinkers before OLT. Ten patients were immunosuppressed with CyA and 5 with tacrolimus. Acute rejection episodes before tumor diagnosis occurred in 6 patients (40%). Two patients underwent thoracotomy, but only one was resected. The remaining 13 patients were unresectable because of locally advanced tumor or metastatic disease. Two unresectable patients received palliative chemotherapy. All patients died with a mean survival from tumor diagnosis, of 5.3 months (range, 3 days to 33 months). CONCLUSION: A significantly higher incidence of lung tumors was observed among patients who underwent OLT for alcoholic cirrhosis, usually diagnosed in advanced stages of poor prognosis and low survival.