Daclatasvir and Sofosbuvir With or Without Ribavirin in Liver Transplant Recipients: A Single-Center Real-World Study.

BACKGROUND: Treatment with direct-acting antiviral drugs in interferon-free regimens is currently recommended for viral hepatitis C recurrence after liver transplantation. There are limited data regarding its results in this population, and no optimal treatment scheme has yet been singled out. METHODS: We report our real-world results in liver transplant (LT) recipients. All patients were hepatitis C virus (HCV) monoinfected and completed a 12-week treatment course, followed 12 weeks later by HCV polymerase chain reaction testing with 12 IU/mL sensibility. Liver fibrosis was graded with the use of biopsies taken <12 months before treatment and stratified as early (0-1) or moderate to advanced (2-4) according to the Metavir score. RESULTS: Median postoperative time was 5.2 years. Genotype 3 was found in 66.7% of the sample. The following regimens were prescribed: daclatasvir-sofosbuvir with (n = 11) or without (n = 28) ribavirin. Genotypes 1 and 3 were evenly distributed between the regimens. Sustained virologic response (SVR) was obtained in 24 out of 28 patients (85.7%) who received daclatasvir-sofosbuvir and in all patients (100%) who received daclatasvir-sofosbuvir-ribavirin (global SVR 89.7%). All patients that failed treatment had genotype 3 HCV. Fibrosis was evaluated in 79.5% of the sample: 48.4% had early and 51.6% had moderate to advanced fibrosis, for which ribavirin was more commonly prescribed (P = .001). CONCLUSIONS: The SVR rate in our LT recipients was similar to that previously reported in the literature. The addition of ribavirin to DAA treatment appears to be justified in this population.

Comparison Between IGL-1 and HTK Preservation Solutions in Deceased Donor Liver Transplantation.

The effectiveness of liver preservation solutions remains in evidence. Cold ischemia time, steatosis, expanded criterion donors, operational cost, and survival represent important roles in its success. In a prospective cohort study between August 2009 and April 2014, 178 patients were allocated into an Institut Georges Lopez - 1 (IGL-1) solution group (63.5%) or histidine-tryptophan-ketoglutarate (HTK) group (36.5%). There were no differences among recipient's characteristics including age, skin color, gender, Model for End-stage Liver Disease score, acute rejection, cholestasis, and reperfusion syndrome incidences. Also, donors, age average, skin color, donor risk index, time in intensive care unit, hemodynamic variables, infections, and steatosis incidences were similar. The average cold ischemia time was 494 minutes in the IGL-1 group and 489 minutes in the HTK group (P = .77). Alanine aminotransferase and aspartate aminotransferase serum levels on the first postoperative day were 707 and 1185 mg/dL, respectively, with IGL-1 and 1298 and 2291 mg/dL, respectively, with HTK (P = .016) and similar at day 15 (P > .88). The incidence of delayed graft function was 4.5% with IGL-1 and 4.6% with HTK (P = .90). The incidence primary nonfunction was 2.7% with IGL-1 and 3.1% with HTK (P = .71). The incidence of perioperative death was 11.5% with IGL-1 and 13.8% with HTK (P = .94). The survival in 30 months was 86% in IGL-1 group and 82% in HTK group (P = .66). Both preservation solutions are efficient to liver transplantations with deceased donors. Major prospective trials are necessary to evaluate each preservation solution's particularities. The preservation solution availability in each transplantation center must guide its use at the present moment.

Acute kidney injury after liver transplantation: incidence and mortality.

INTRODUCTION: Patients undergoing orthotopic liver transplantation often present with acute kidney injury (AKI) in the postoperative period. It has been associated with a greater number of complications and high mortality rates. The goal of this study was to determine the incidence of AKI during the early posttransplant period and mortality in patients undergoing orthotopic liver transplantation in our hospital. PATIENTS AND METHODS: In this retrospective cohort study, we reviewed the medical records of all patients aged >18 years undergoing liver transplantation from April 2008 to April 2011. The exclusion criteria were a glomerular filtration rate (estimated by using the Modification of Diet in Renal Disease formula) <60 mL/min/1.73 m(2) or AKI at the time of transplantation. AKI was defined as an increase ≥50% from preoperative baseline serum creatinine levels during the hospitalization period. RESULTS: Of 113 selected patients, 78 (69%) were male. The mean age was 54.03 ± 9.38 years. The mean preoperative baseline creatinine level was 0.94 ± 0.15 mg/dL, and the estimated glomerular filtration rate was 87.09 ± 19.67 mL/min/1.73 m(2). The mean calculated Model for End-Stage Liver Disease score was 13. Hepatitis C serology was present in 70.8%, hepatitis B in 11.5%, hepatocellular carcinoma in 75.2%, and alcohol abuse in 31.9% of patients. The incidence of AKI was 56.6% (64 of 113 patients). The main risk factors for AKI were Model for End-Stage Liver Disease score and diuretic use at baseline. Renal replacement therapy (RRT) was performed in 19.5% (22 of 113) of patients. The hospital mortality rate in the group with AKI was 25% (16 of 64 patients) and 6.1% (3 of 49 patients) between patients without AKI (odds ratio, 5.11 [confidence interval, 1.39-18.7]; P < .01]. Among patients who underwent RRT, the in-hospital mortality rate was 54.5% (12 of 22 patients) compared with 7.7% (7 of 91 patients) from the other remaining patient cohort (odds ratio, 14.40 [confidence interval, 4.60-45.00]; P < .01). CONCLUSIONS: There was a high incidence of AKI in patients undergoing liver transplantation and an increased risk of mortality among patients who needed RRT.

Randomized clinical assay for hepatic grafts preservation with University of Wisconsin or histidine-tryptophan-ketoglutarate solutions in liver transplantation.

University of Wisconsin (UW) solution has been the standard for preservation of liver transplantation grafts since 1989. However, some studies demonstrated that histidine-tryptophan-ketoglutarate (HTK) solution is also effective. The purpose of this study was to compare the efficacy of both solutions in liver transplantation. From January 2003 to August 2004 the livers of deceased donors were randomized into HTK and UW groups. The 102 studied patients included 65 (63.7%) in the UW group and 37 (36.3%) in the HTK group. Sex, race, hemodynamic state, use of adrenergic drugs, and presence of steatosis in the donor were similarly distributed in the two groups (P > .05). The mean age of the donors was 38.1 years (SD +/-14.4) in the UW group and 44.6 years (SD +/-14.2) in the HTK cohort (P = .036). Sex, race, age, etiology of the cirrhosis, retransplant, acute liver failure, portal thrombosis, and Child-Pugh and MELD scores in the recipients were similarly distributed in the two recipient samples (P > .05). Among 89 patients who completed 4 months of follow-up, the HTK group included eight cases (25.8%) of biliary complications versus five cases (8.6%) in the UW group (P = .033; OR = 2.0 95% CI = 1.2-3.5). The incidence of graft dysfunction was 2.8% in the HTK group and 9.4% in the UW group (P = .15). In conclusion, UW and HTK solutions were equally effective for the preservation of the hepatic graft. The routine use of HTK solution can reduce the costs of liver transplantation.

Risk factors associated with cytomegalovirus infection in orthotopic liver transplant patients.

UNLABELLED: Our objective was to investigate the potential risk factors associated with cytomegalovirus (CMV) infection. PATIENTS AND METHODS: From January 1999 to December 2001, 163 liver transplantations were performed in 154 patients. The study inclusion criteria were absence of retransplantation and survival of more than 6 months. One hundred fifteen patients met the inclusion criteria. We determined variables such as age, gender, and number of hemecomponents as well as serum IgG CMV status of donors and recipients. We recorded the immunosuppression used by each patient. CMV infection was detected by positive antigenemia. RESULTS: Recipient mean age was 50 years. The etiology of cirrhosis was viral (n = 57; 49.6%), alcoholic (n = 20; 17.4%), virus and alcohol (n = 15; 13.0%), cryptogenic (n = 14; 12.2%), or other causes (n = 9; 7.8%). CMV infection was positive in 75 patients (65.8%). There was no relation between infection and age, gender, or CMV IgG donor recipient status, or the number of hemecomponent units. The risk was 3.8-fold higher for patients receiving a three-drug compared with a two-drug regimen. When cyclosporine was used instead of tacrolimus, the risk of CMV infection was 4.3-fold higher. Logistic regression analysis revealed cyclosporine (OD=5.8) and a three-drug regimen (OD=6.7) to have stronger associations with CMV infection. CONCLUSION: The use of cyclosporine (OD=5.8) and a three-drug regimen (OD=6.7) are risk factors for CMV infection.

Impact of cytomegalovirus infection on long-term survival after orthotopic liver transplantation.

UNLABELLED: Cytomegalovirus (CMV) is one of the most common and serious opportunistic infections in solid organ transplant patients. In different series the incidence of CMV infection ranges from 25% to 85%. An indirect effect of infection includes reduced long-term patient and allograft survival. Our objective was to determine the relationship between CMV infection and patient survival after orthotopic liver transplantation. PATIENTS AND METHODS: From January 1999 to December 2001, 163 orthotopic liver transplantations were performed in 154 patients. The inclusion criteria for this analysis were the absence of retransplantation and survival of more than 6 months. One hundred fifteen patients met the inclusion criteria. CMV infection was detected by positive antigenemia. RESULTS: CMV infection occurred in 65.8% of patients after orthotopic liver transplantation. Their 5-year survival was 85%, with no difference observed between patients with or without infection (P = .8). CONCLUSION: CMV infection did not interfere with patient survival after orthotopic liver transplantation.

Enteric-coated mycophenolate sodium experience in liver transplant patients.

Mycophenolate sodium (EC-MPS) has been shown to be as effective and as safe as mycophenolate mofetil (MMF) in renal transplant patients. Nevertheless, compared to MMF its use in liver transplant patients has been limited. The purpose of this study was to analyze the efficacy of EC-MPS as a primary immunosuppressant or as a replacement for MMF in liver transplant patients. Ninety among 470 liver transplant recipients were receiving or had added an antimetabolite to their immunosuppressant therapy. The most common reason for this change was renal dysfunction (47.8%) or diabetes (32.2%). EC-MPS was started at a median of 30 months after liver transplantation. The mean administered daily dose was 720 mg/d. At least one gastrointestinal symptom was reported by 25 patients. Abdominal pain (16.6%) and diarrhea (14.5%) were the most frequent. EC-MPS had to be discontinued in two patients, while six others required dose reduction to resolve the symptoms. Hematological adverse events were infrequent: three patients had leukopenia and one, anemia, all of which responded to dosage reduction. There was a creatinine reduction within 6 months of drug commencement and maintenance of the lower creatinine levels at 1 year among patients who began EC-MPS for renal dysfunction. Serum low-density lipoprotein cholesterol and triglyceride levels were significantly lower among patients on EC-MPS than on MMF. In conclusion, EC-MPS appears to have a similar efficacy and safety profile as MMF in liver transplant patients. Hematological and gastrointestinal adverse events were infrequent; seldom had the drug to be discontinued.

Oxidative stress, hepatocellular integrity, and hepatic function after initial reperfusion in human hepatic transplantation.

BACKGROUND: The mechanisms underlying liver graft dysfunction are not completely defined, although much of the injury derives from oxidative stress in organ reperfusion. The antioxidant glutathione in its reduced form (GSH) is an important agent to detoxify oxygen species after reperfusion. However, this effect might be limited by low concentrations at the end of cold storage. The objective of this study was to evaluate GSH and glutathione oxidized (GSSG) hepatic levels pre- and postreperfusion and correlate with hepatocellular injury and liver function in the 5 subsequent days after transplantation. METHODS: Liver biopsies were taken immediately before implant and 2 hours after venous reperfusion in 34 grafts, determining GSH, GSSG levels, and GSSG/GSH ratio. Aminotransferases (ALT, AST) and PT were measured for 5 days. RESULTS: There was a strong decrease in GSH concentration (P <.0001), increase of GSSG levels (P <.01), and increase of the GSSG/GSH ratio (P <.0001). No correlations were found between GSH, GSSG, or GSH/GSSH levels and AST, ALT, and PT. CONCLUSION: Glutathione levels showed significant changes after 2 hours of reperfusion, due to intense oxidative stress. Therapies to replenish GSH should be considered as a protective measure to avoid liver graft dysfunction after transplantation.

Management of vascular complications after pediatric liver transplantation.

Sixty-five children underwent liver transplantation (LTx) from March 1995 to December 2002. Cirrhosis due to biliary atresia was the main indication, and hepatic artery thrombosis (HAT) the most common vascular complication (n = 5). Other vascular problems were portal vein thrombosis and stenosis. Another patient developed hepatomegaly and ascites due to a late stenosis of the left hepatic vein anastomosis. The two cases of venous stenosis were successfully treated by percutaneous angioplasty. One graft with HAT was saved, but four children died awaiting retransplant.

Risk factors associated with cytomegalovirus-positive antigenemia in orthotopic liver transplant patients.

The aim of the study was to investigate risk factors associated with cytomegalovirus (CMV)-positive antigenemia in orthotopic liver transplant (OLT) patients. Sixty-nine patients undergoing OLT during 2001 were retrospectively evaluated for CMV antigenemia during a follow-up of 6 months after transplantation for demographic variables, pretransplant donor and recipient CMV serologic status, etiology of liver disease, number of blood transfusions, and type of immunosuppression. Among the 69 patients who underwent 71 OLT in this period, 43 met study criteria. Mean age was 49.7 +/- 10.8 years and 60.5% were men. End-stage liver disease was the indication for liver transplant, except in one case. The most prevalent etiology of liver disease was hepatitis C and/or alcohol in 66% of the cases. CMV-positive status was recorded in 74% of donors and 95% of recipients. None of the CMV-negative recipients received a positive donor allograft. CMV-positive antigenemia was 84% with 12% having two episodes of infection. There was no correlation between CMV infection and age, gender, etiology of liver disease, or number of blood transfusions. However, all patients using cyclosporine had CMV-positive antigenemia compared with 61% using tacrolimus (P <.032). In this study, the incidence of CMV infection after OLT in adult patients was slightly higher than reported in literature. No risk factor was associated with CMV antigenemia; however, this study suggests a higher probability of CMV infection among patients treated with cyclosporine.

[Neurologic disorders in patients submitted to liver transplantation: analysis of 30 consecutive cases]. / Alterações neurológicas em pacientes submetidos a transplante hepático: análise de 30 casos consecutivos.

Neurologic complications are important source of morbi-mortality, in liver transplantation. They result from previous factors, alterations during the surgical procedure, effects from immunosuppressor drugs, coagulopathy and infections. We analyzed, retrospectively, the chronology, causes, and frequencies of neurologic alterations in thirty adult patients submitted to liver transplantation, and our results differ slightly from those registered in other series.

[Follow-up of pediatric patients evaluated for liver transplantation]. / Evolução dos pacientes pediátricos avaliados para transplante hepático.

OBJECTIVE: To analyze the evolution of pediatric patients chosen for hepatic transplantation. METHODS: A review was made of the clinical charts of the first 65 children and adolescents with chronic liver disease, aged 5 months to 19 years (X = 6.8%), chosen for liver transplantation during the period of August 1994 to March 1996. Data refer to the patients' demographic characteristics, etiology of their liver disease, their psychosocial situation and of their parents, and their clinical and laboratorial evaluation. According to the severity of the disease, patients were classified as active (waiting for a donor), in evaluation, inactive (compensated liver disease), and excluded for psychosocial or medical conditions, or because of bad indication. RESULTS: Eight patients (12%) received transplantation, and one of them died. Seven (11%) died when in evaluation or waiting for a donor. Ten patients (15%) were excluded from the waiting list: 6 for social problems, and 4 for medical problems. No patient was excluded for bad indication. Six patients are in the active list, waiting for donor. The other 23 patients (35%) are in evaluation, and 11 (17%) are classified as inactive in the waiting list. CONCLUSIONS: Eleven patients (17%) were not operated on due to the advanced stage of the liver disease. We emphasize the necessity of organ donation, and the early contact of the patients with a reference center.