Fibrosing Cholestatic Hepatitis C After Liver Transplantation: Therapeutic Options Before and After Introduction of Direct-Acting Antivirals: Our Experience and Literature Review.

BACKGROUND: Cirrhosis caused by hepatitis C is the most common indication for liver transplantation. The most aggressive form of hepatitis C virus (HCV) relapse after liver transplantation is fibrosing cholestatic hepatitis C, which can be observed in 2% to 15% of recipients. METHODS: Double therapy with peg-interferon and ribavirin was characterized by low antiviral response, rapid fibrosis, and frequent graft failure within 1 year after surgery. RESULTS: Introduction of direct-acting antivirals for HCV treatment allows for more efficient therapy with less adverse reactions, including patients with fibrosing cholestatic hepatitis C. CONCLUSIONS: We present 4 (2.5%) cases of cholestatic viral hepatitis C recurrence in patients undergoing transplantation between 2006 and 2015 at the Transplantation Institute of Warsaw; during this period, 158 liver transplants were performed in patients with cirrhosis caused by HCV infection.

Dynamic Elastography in Diagnostics of Liver Fibrosis in Patients After Liver Transplantation Due to Cirrhosis in the Course of Hepatitis C.

BACKGROUND: Assessment of the dynamics and degree of liver fibrosis in patients after liver transplantation is a basic element in the process of determining transplant survival prognosis. It allows planning and early initiation of prophylaxis or treatment, which translates into increased chances of preventing cirrhosis and of long-term optimal function of the graft. The aim of this study was to compare the results of biopsy and dynamic elastography in diagnostics of transplanted liver fibrosis, as well as determination of the stiffness cut-off point for assessment of significant fibrosis. PATIENTS AND METHODS: The study included 36 patients who had undergone liver transplantation due to cirrhosis in the course of hepatitis C virus (HVC) infection. Fibrosis was assessed in bioptates according to the METAVIR score (F0-F4). Elastography was performed using FibroScan; receiver operating characteristic curve analysis was used to identify the cut-off point for significant fibrosis (≥F2). RESULTS: The median stiffness in kPa for the whole group F0-F4 was 6.3 (range 3.4-29.9); for ≥F2 it was 6.9 (3.4-29.9), whereas for F0-F1 it was 4.4 (3.5-8.0). It was demonstrated that the value of 4.7 kPa in elastography is a statistically significant cut-off point for differentiation between the groups F0-F1 and F2-F4 (sensitivity: 93%, specificity: 57%, positive predictive value: 90%, negative predictive value: 66%), area under the receiver operating characteristic curve: 0.746 (95% confidence interval: 0.53-0.95, P < .05). CONCLUSIONS: Elastography is a promising tool for noninvasive assessment of significant liver fibrosis in patients after transplantation due to cirrhosis in the course of hepatitis C; it allows reduction in the number of biopsies performed.

Left ventricular hypertrophy in renal transplant recipients in the first year after transplantation.

BACKGROUND: Left ventricular hypertrophy (LVH) is a significant risk factor for cardiovascular complications in renal transplant recipients. The study objective here was to assess LVH and related factors in renal transplant recipients in the 1st year after transplantation. METHODS: Echocardiographic examinations were performed in the early post-transplantation period in 43 patients (age, 43.9 ± 12.4 years; male, 53.5%) and at 1 year after transplantation in 40 patients. At the same time, basic blood tests, N-terminal pro-B-type natriuretic peptide (NT-proBNP) level tests, and ambulatory blood pressure measurements were performed. LVH was diagnosed when LV mass index was >95 g/m(2) in women and >115 g/m(2) in men. Statistical analyses were performed with the use of the R Package. RESULTS: LVH (mainly concentric) was found in 51.2% of the patients in the early period and in 50% of the patients at 1 year. In 30% of the patients with baseline LVH it regressed at 1 year and in another 30% LVH developed de novo. In the early period, LV mass was influenced by age, sex, body mass index (BMI), estimated glomerular filtration rate (eGFR), and a history of cardiovascular disorders during dialysis therapy, whereas at 1 year after transplantation it was influenced by age, sex, BMI, 24-hour systolic blood pressure, a history of hypertension during dialysis therapy, and abnormal 24-hour blood pressure profile. Weight gain interfered with LVH regression during the 1st year after transplantation, whereas no improvement in blood pressure control contributed to de novo development of LVH. All other patients (those without LVH) had a morphologic abnormality of the left ventricle, the so-called concentric remodeling. Higher NT-proBNP levels were observed in patients with LVH. CONCLUSIONS: LVH is present in one-half of renal transplant recipients in the 1st year after transplantation, and concentric remodeling is present in the remaining patients of this group. An echocardiographic examination is indicated in every renal transplant recipient. Measurements of NT-proBNP levels are helpful in LVH diagnostics.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) assessment in the first year after renal transplantation and its relationship with graft function and left ventricular hypertrophy.

BACKGROUND: NT-proBNP is a natriuretic neurohormone released mainly from ventricular cardiomyocytes in conditions of volumetric or pressure overload; it is suitable for use as a marker of left ventricular hypertrophy (LVH), a common disorder in renal transplant recipients. The study objective here was to assess NT-proBNP levels in the 1st year after renal transplantation (RT) and its relationship with graft function and LVH. METHODS: Sixty patients (age, 49 ± 16.9 y; male, 58%) were subjected to prospective 1-year follow-up. Basic blood tests and NT-proBNP level measurements were performed twice (in the early period and at 1 year after transplantation). Cardiac echography was performed in 40 patients. LVH was diagnosed when left ventricular mass index was >95 g/m(2) in women and >115 g/m(2) in men. Statistical analyses were performed with the use of the R Package. RESULTS: At 1 year after RT, the NT-proBNP level decreased >2-fold compared with the early period (median 171 pg/mL [interquartile range (IQR), 104.5-283] vs 368 pg/mL[IQR, 170-629]; P = .00008). In the early post-transplantation period, NT-proBNP correlated with the patient's age, body mass index, estimated glomerular filtration rate (eGFR), and left ventricular end-diastolic dimension, and at 1 year after transplantation its correlation with the eGFR range (patients with eGFR ≥60 mL min(-1) 1.73 m(-2) had significantly lower NT-proBNP levels than those with eGFR <60 mL min(-1) 1.73 m(-2)), with age,and with ejection fraction was found. Patients with LVH had higher NT-proBNP levels than those without LVH in the early period (median 511 pg/mL [IQR, 190-736] vs 380 pg/mL [IQR, 217-511]; P = .09), and at 1 year (median 269 pg/mL [IQR, 155-474] vs 133 pg/mL [IQR, 99-134]; P = .057). At NT-proBNP >480 pg/mL in the early period and >280 pg/mL at 1 year, LVH occurred with a 68% probability (P = .05 and P = .03, respectively). CONCLUSIONS: During the 1st year after RT, NT-proBNP levels decrease ≥2-fold and are primarily related to eGFR. NT-proBNP measurements are useful in identifying patients with LVH.

Dramatic recurrence of cancer in a patient who underwent kidney transplantation--case report.

BACKGROUND: Besides cardiovascular diseases and infections, cancers are the main cause of death in patients after transplantation of a vascularized organ. After transplantation, usually de novo cancers develop. Recurrences of cancers that had been diagnosed and treated before transplantation are much rarer. In exceptional cases, cancer is transferred with the donor's organ. The epidemiology and the course of post-transplantation de novo neoplasia is relatively well known. However, the issue of recurrence of pre-transplantation cancer, which is significantly rarer and its course more individualized and difficult to predict, poses a challenge to contemporary transplantation. CASE REPORT: This paper presents an unexpectedly rapid recurrence of rare cancer-endometrial stromal sarcoma-that occurred shortly after transplantation of a kidney from a deceased donor to a patient who had undergone cancer treatment 7 years earlier. The dramatic course of the disease, complicated with recurrent massive thrombosis of the inferior vena cava and the right cardiac cavities, as well as pulmonary embolism and serious infectious complications, illustrates the difficulties related to qualifying patients with a history of malignancy for transplantation. CONCLUSIONS: Based on this case report, we attempt to find an answer to the question about the risk of cancer recurrence in patients receiving immunosuppressive therapy and find out how it can be minimized. Answering these questions is particularly important if the recurrent cancer is substantially more aggressive, cancer treatment options are limited, and the prognosis is poor due to lack of immunocompetence.

Multidrug resistance-associated protein 2 gene (ABCC2) variant in kidney allograft recipients.

Multidrug resistance-associated proteins may play crucial roles in the protection of internal organs, particularly the kidneys and liver, from various toxic agents. Little is known about their significance in transplanted organ function and survival. The aim of the present study was to evaluate the frequency of functional ABCC2 4544A>G polymorphism in 165 renal transplant recipients. DNA was isolated from peripheral blood and ABCC2 4544A>G polymorphism was assessed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Analysis of allele and genotype frequencies revealed that the presence of ABCC2 4544 A allele was associated with prolonged observation time and may have an impact on a greater frequency of proteinuria. This observation strongly suggested that particular alleles of the ABCC2 gene may contribute to transplantation outcomes.

Factors predisposing to urinary tract infections in adult kidney allograft recipients with lower urinary tract reconstruction.

OBJECTIVE: Urinary bladder augmentation or urinary diversion may be necessary for successful kidney transplantation in cases of serious urinary tract dysfunction. Patients with reconstructions of the urinary collecting system show noninferior graft survival, although urinary tract infections (UTI) may threaten kidney and recipient survivals. Herein we sought to identify risk factors for serious UTIs in cases of urinary collecting system reconstructions and to evaluate kidney survival and function. PATIENTS AND METHODS: This prospective, case-controlled study included 24 kidney allograft recipients with urinary tract reconstructions who were engrafted from 1999 to 2008. As controls we selected recipients of standard kidney transplants who were matched (1:3) for sex, age, donor type, procedure date, and immunosuppressive regimen. RESULTS: At posttransplantation 33.6 +/- 28 months follow-up, kidney allograft survival was 83% among the reconstructed and 97% among the control groups (P = NS). Kidney allograft function at 3 months in the reconstruction group showed estimated glomerular filtration rate (eGFR) calculated by the Cockcroft-Gault (C-G) equation of 70.4 +/- 20.8 vs 78.8 +/- 19.2 mL/1.73 m(2) in controls (P = .39), and at the end of follow-up, 66.3 +/- 18.1 vs 77.1 +/- 18.9 mL/1.73 m(2), respectively (P = .26). Urinary tract reconstruction patients experienced UTI in 91.7% of cases (n = 22) vs 45.6% in controls (n = 31; P < .0001). A necessity for in-hospital treatment was observed in 67% vs 28% of cases (P < .001). Urosepsis occurred in 4 study patients and 4 controls (P = NS). We observed an increased risk for serious UTI and a trend to diminished graft function (odds ratio [OR] = 1.6 per 10 ml/min of eGFr C-G; 95% confidence interval (CI) 0.97-2.77; P = .055; and OR = 14.7 per 1 mg/dL of serum creatinine; 95% CI 0.61-352.3; P = .097). Another predictor for UTI was cytomegalovirus disease (CMV). CONCLUSION: Kidney recipients requiring urinary tract reconstructions additionally benefit from obtaining the best quality allografts and CMV prophylaxis.