Search

Background and Aims: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplant (post-LT) outcomes in Europe., Approach and Results: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years, with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%)., Conclusions: LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Long-term humoral immunity and its protective role in liver transplantation (LT) patients have not been elucidated. We performed a prospective multicenter study to assess the persistence of immunoglobulin G (IgG) antibodies in LT recipients 12 months after coronavirus disease 2019 (COVID-19). A total of 65 LT recipients were matched with 65 nontransplanted patients by a propensity score including variables with recognized impact on COVID-19. LT recipients showed a lower prevalence of anti-nucleocapsid (27.7% versus 49.2%; P = 0.02) and anti-spike IgG antibodies (88.2% versus 100.0%; P = 0.02) at 12 months. Lower index values of anti-nucleocapsid IgG antibodies were also observed in transplantation patients 1 year after COVID-19 (median, 0.49 [interquartile range, 0.15-1.40] versus 1.36 [interquartile range, 0.53-2.91]; P < 0.001). Vaccinated LT recipients showed higher antibody levels compared with unvaccinated patients (P < 0.001); antibody levels reached after vaccination were comparable to those observed in nontransplanted individuals (P = 0.70). In LT patients, a longer interval since transplantation (odds ratio, 1.10; 95% confidence interval, 1.01-1.20) was independently associated with persistence of anti-nucleocapsid IgG antibodies 1 year after infection. In conclusion, compared with nontransplanted patients, LT recipients show a lower long-term persistence of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, SARS-CoV-2 vaccination after COVID-19 in LT patients achieves a significant increase in antibody levels, comparable to that of nontransplanted patients., (© 2021 by the American Association for the Study of Liver Diseases.)

Cardiovascular (CV) diseases are recognized longterm causes of death after liver transplantation (LT). The objective of this multicenter study was to analyze the prevalence and the evolution of CV risk factors and CV morbidity and mortality in 1819 LT recipients along 5 years after LT. The influence of baseline variables on survival, morbidity, and mortality was studied. There was a continuous and significant increase of the prevalence of all the CV risk factors (except smoking) after LT. CV diseases were the fourth cause of mortality in the 5 years after LT, causing 12% of deaths during the follow-up. Most CV events (39%) occurred in the first year after LT. Preexisting CV risk factors such as age, pre-LT CV events, diabetes, metabolic syndrome, and hyperuricemia, and mycophenolate-free immunosuppressive therapy, increased post-LT CV morbidity and mortality. The development of new-onset CV risk factors after LT, such as dyslipidemia and obesity, independently affected late CV morbidity and mortality. Tacrolimus and steroids increased the risk of posttransplant diabetes, whereas cyclosporine increased the risk of arterial hypertension, dyslipidemia, and metabolic syndrome. In conclusion, CV complications and CV mortality are frequent in LT recipients. Preexisting CV risk factors, immunosuppressive drugs, but also the early new onset of obesity and dyslipidemia after LT play an important role on late CV complications. A strict metabolic control in the immediate post-LT period is advisable for improving CV risk of LT recipients. Liver Transplantation 23 498-509 2017 AASLD., (© 2017 by the American Association for the Study of Liver Diseases.)

A national, multicenter, retrospective study was conducted to assess the results obtained for liver transplant recipients with conversion to everolimus in daily practice. The study included 477 recipients (481 transplantations). Indications for conversion to everolimus were renal dysfunction (32.6% of cases), hepatocellular carcinoma (HCC; 30.2%; prophylactic treatment for 68.9%), and de novo malignancy (29.7%). The median time from transplantation to conversion to everolimus was 68.7 months for de novo malignancy, 23.8 months for renal dysfunction, and 7.1 months for HCC and other indications. During the first year of treatment, mean everolimus trough levels were 5.4 (standard deviation [SD], 2.7) ng/mL and doses remained stable (1.5 mg/day) from the first month after conversion. An everolimus monotherapy regimen was followed by 28.5% of patients at 12 months. Patients with renal dysfunction showed a glomerular filtration rate (4-variable Modification of Diet in Renal Disease) increase of 10.9 mL (baseline mean, 45.8 [SD, 25.3] versus 57.6 [SD, 27.6] mL/minute/1.73 m(2) ) at 3 months after everolimus initiation (P < 0.001), and 6.8 mL at 12 months. Improvement in renal function was higher in patients with early conversion (<1 year). Adverse events were the primary reason for discontinuation in 11.2% of cases. The probability of survival at 3 years after conversion to everolimus was 83.0%, 71.1%, and 59.5% for the renal dysfunction, de novo malignancy, and HCC groups, respectively. Everolimus is a viable option for the treatment of renal dysfunction, and earlier conversion is associated with better recovery of renal function. Prospective studies are needed to confirm advantages in patients with malignancy., (© 2015 American Association for the Study of Liver Diseases.)

This open-label, randomized study compared the efficacy of a regimen of corticosteroids and tacrolimus (standard therapy group, n = 79) with a regimen of daclizumab induction therapy in combination with mycophenolate mofetil and tacrolimus (modified therapy group, n = 78) in primary liver transplant recipients. The primary endpoint was biopsy-proven acute rejection (BPAR) at 24 weeks. Secondary endpoints included time to rejection and patient and graft survival. The incidence of BPAR was significantly reduced in the modified therapy group compared to the standard therapy group (11.5% versus 26.6%, respectively, P = 0.017). The time to rejection was significantly shorter in the standard therapy group compared with the modified therapy group (P = 0.044). There was no significant difference between groups in patient or graft survival. Hepatitis C virus-positive patients exhibited no differences from hepatitis C virus-negative patients with respect to the incidence of BPAR. A steroid-sparing regimen of daclizumab, mycophenolate mofetil, and tacrolimus was effective and well tolerated in the prevention of BPAR in adult liver transplant recipients in comparison with a standard regimen of tacrolimus and steroids.

Surgical site infections are common bacterial infections in orthotopic liver transplantation. The purpose of this study was to determine the incidence, timing, location, and risk factors, specifically antibiotic prophylaxis, for surgical site infections. A prospective study was performed that included a population of 1222 consecutive patients (73.0% males) who underwent liver transplantation in Spanish hospitals belonging to the Red de Estudio de la Infección en el Trasplante research network. One hundred seven patients developed surgical site infections. The predominant infection sites were incisional wound (53 episodes) and peritonitis (40 episodes). The timing of the organ/space surgical site infections was slightly delayed in comparison with incisional surgical site infections. Enterococcus spp., Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii were the predominant pathogens. Choledochojejunal or hepaticojejunal reconstruction (odds ratio, 4.2; 95% confidence interval, 1.6-10.7), previous liver or kidney transplant (odds ratio, 2.6; 95% confidence interval, 1.1-6.3), and more than 4 red blood cell units transfused (odds ratio, 2.0; 95% confidence interval, 1.1-3.4) were independently associated with the development of surgical site infections. Biliary reconstruction by choledochojejunostomy or hepaticojejunostomy increases the risk of surgical site infections.

Orthotopic liver retransplantation (re-OLT) is highly controversial. The objectives of this study were to determine the validity of a recently developed United Network for Organ Sharing (UNOS) multivariate model using an independent cohort of patients undergoing re-OLT outside the United States, to determine whether incorporation of other variables that were incomplete in the UNOS registry would provide additional prognostic information, to develop new models combining data sets from both cohorts, and to evaluate the validity of the model for end-stage liver disease (MELD) in patients undergoing re-OLT. Two hundred eighty-one adult patients undergoing re-OLT (between 1986 and 1999) at 6 foreign transplant centers comprised the validation cohort. We found good agreement between actual survival and predicted survival in the validation cohort; 1-year patient survival rates in the low-, intermediate-, and high-risk groups (as assigned by the original UNOS model) were 72%, 68%, and 36%, respectively (P <.0001). In the patients for whom the international normalized ratio (INR) of prothrombin time was available, MELD correlated with outcome following re-OLT; the median MELD scores for patients surviving at least 90 days compared with those dying within 90 days were 20.75 versus 25.9, respectively (P =.004). Utilizing both patient cohorts (n = 979), a new model, based on recipient age, total serum bilirubin, creatinine, and interval to re-OLT, was constructed (whole model chi(2) = 105, P <.0001). Using the c-statistic with 30-day, 90-day, 1-year, and 3-year mortality as the end points, the area under the receiver operating characteristic (ROC) curves for 4 different models were compared. In conclusion, prospective validation and use of these models as adjuncts to clinical decision making in the management of patients being considered for re-OLT are warranted.

Acute graft rejection remains a major problem among additional sequelae in liver transplant recipients. Basiliximab, a chimeric monoclonal antibody with high affinity for the CD25 chain of the interleukin-2 receptor, has significantly reduced the incidence of acute rejection episodes in renal transplant recipients. This single-arm, open-label, multicenter study investigated the efficacy and tolerability of basiliximab immunoprophylaxis in adult patients undergoing first elective liver transplantation. One hundred one patients (70 hepatitis C virus [HCV]-negative patients, 31 HCV-positive patients) were administered basiliximab, 20 mg, by intravenous bolus injection the day of transplantation (day 0) and day 4. In addition, all patients were administered triple immunosuppressive therapy with cyclosporine, steroids, and azathioprine. The efficacy of basiliximab was assessed by conventional parameters, and tolerability was assessed by the incidence of adverse events, infections, and laboratory test result abnormalities. At 6 months, the incidence of first acute biopsy-confirmed rejection episodes was 22.8%. Rejections were more frequent in the HCV-positive (29.0%) than HCV-negative subgroup (20.0%; P =.441). No rejection episode was graded histologically as severe, and no patient required antibody therapy for the management of acute rejection. Ten patients (9.9%) required treatment with tacrolimus for acute rejection episodes. Patient and graft survival rates at 12 months were 90.1% and 88.1%, respectively. Basiliximab caused no injection-site reactions, anaphylaxis, or cytokine release syndrome. Five malignancies were reported at 12 months: of these, three malignancies predated transplantation surgery. Compared with earlier studies, the addition of basiliximab immunoprophylaxis to triple immunosuppressive therapy provides increased efficacy in reducing the incidence of acute rejection episodes, with no clinically significant increase in adverse events.

Arterial hypertension is commonly observed in orthotopic liver transplantation (OLT) recipients receiving cyclosporin A (CsA), but the precise pathogenetic mechanisms remain partially unknown. The aim of this study was to investigate endothelium-dependent and -independent dilation and adrenergic constriction of resistance vessels of OLT recipients treated with CsA. Vascular reactivity was examined in 22 OLT patients, 10 with and 12 without arterial hypertension, and in 10 control subjects by assessing the forearm blood flow response to the brachial artery infusion of increasing concentrations of methacholine chloride, sodium nitroprusside, and phenylephrine. In 10 OLT patients, the response to methacholine was also examined after acetylsalicylate. The ratio of serum nitrite and nitrate to serum creatinine was lower (P < .05) in OLT patients with hypertension than in nonhypertensive patients and controls. Basal forearm flow was similar in the three groups. Methacholine vasodilation was impaired in the hypertensive patients as shown by a lower maximum forearm vasodilator response and a shift in the dose response curve to methacholine to the right compared with the nonhypertensive OLT patients and the controls. The response to methacholine was not modified after salicylate. Forearm flow response to nitroprusside was similar in the three groups. No differences between the patients and the controls were found in the maximum forearm flow contraction in response to phenylephrine. An impairment in endothelium-dependent vasodilation could mediate arterial hypertension in OLT patients immunosuppressed with CsA.

Twenty-seven clinical and laboratory data and the subsequent clinical course of 93 consecutive adult patients who underwent orthotopic liver transplantation for various chronic advanced liver diseases were analyzed retrospectively to assess the risk factors of early major bacterial infection and death after the procedure. Forty-one patients (44%) had early major bacterial infection during hospitalization for orthotopic liver transplantation. The mortality rate was 70.7% in patients with early major bacterial infection and was 7.7% in patients without early major bacterial infection (p less than 0.001). Total serum bilirubin, total white blood cell count and polymorphonuclear cell count, IgG (all p less than 0.05) and plasma creatinine level (p less than 0.001) were higher in patients that developed early major bacterial infection than in those who did not. By step-wise discriminant analysis, the strongest risk factor for early major bacterial infection was the serum creatinine level, which achieved an accuracy of 69% for a creatinine level greater than 1.58 mg per dl. Seven variables (ascites, hepatic encephalopathy, elevated white blood and polymorphonuclear cell count, decreased helper to suppressor T cell ratio and elevated plasma creatinine and bilirubin levels) were associated with a significant increased risk for death. A step-wise discriminant analysis of these seven factors resulted in the demonstration of serum creatinine as the greatest risk factor for mortality. A preoperative serum creatinine either less than or greater than 1.72 mg per dl accurately predicts survival or death, respectively, in 79% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred twenty-nine adult patients who received an orthotopic liver transplantation and survived at least 24 hr after surgery were evaluated. During the period of follow-up, 48 of the 129 patients (37%) died. Only 40 of these 48 patients died at our institution and were included in this study. Seventeen of the 40 deaths (42.5%) occurred during the first month after orthotopic liver transplantation and 30 of the 40 deaths (75%) occurred during the first 60 days post-orthotopic liver transplantation. Death was related to infection in 21 cases (52.5%), to multiorgan failure in 8 (20%) and to uncontrollable rejection in 3 (7.6%). The remaining eight deaths (20%) were attributed to a variety of other causes. Eleven of the 21 deaths related to infection (52%) occurred during the first month after orthotopic liver transplantation. Bacterial sepsis was the leading cause of death and accounted for 17 of the 21 deaths (81%) in which infection was present at the time of death. The most frequently isolated bacteria were Pseudomonas and other enteric Gram-negative bacilli. Three patients had complete occlusion of the hepatic artery of the grafted liver. Six patients developed massive infarction of the liver despite patent vascular anastomoses. Histological signs of rejection were seen in 9 of the 31 patients autopsied (29%), but in only 3 of these (9.6%) was rejection the principal cause of death. The biliary anastomoses were patent in all 31 cases examined at autopsy.