Shear Wave Elastography Performance in Noninvasive Assessment of Liver Cirrhosis in Liver Transplant Recipients With the Recurrence of Hepatitis C Infection.

BACKGROUND: The recurrence of hepatitis C (HCV) after liver transplant (LTX) leads to graft fibrosis and cirrhosis. Liver biopsy remains the criterion standard for their diagnosis and monitoring. Our objective was evaluation of shear wave elastography (SWE) in patients with HCV recurrence after LTX and its comparison with histopathologic fibrosis assessment scoring systems. METHODS: A total of 101 LTX recipients with HCV recurrence (42 women [41.6%] and 59 men [58.4%]) were evaluated by graft biopsy specimens (Ishak, Scheurer, and meta-analysis of histologic data in viral hepatitis [Metavir] score) and SWE (liver stiffness). Median age of patients was 59.4 years; median time from LTX was 84.9 months. The study protocol conforms with the Declaration of Helsinki. RESULTS: Median liver stiffness was 21.3 kPa. To differentiate between liver fibrosis and cirrhosis, patients were divided into 2 subgroups: Ishak score fibrosis (1-4 [85.2%]) and cirrhosis (5-6 [13.9%]); Scheurer score fibrosis (0-3 [85.2%]) and cirrhosis (4 [12.9%]); Metavir score fibrosis (0-3 [85.2%]) and cirrhosis (4 [14.9%]). We have observed statistically significant differences between liver fibrosis and liver cirrhosis groups defined on the basis of Ishak, Scheurer, and Metavir scoring systems: 20.8 kPa vs 29.6 kPa (P = .001), 20.7 kPa vs 30.3 kPa (P = .0005), and 20.7 kPa vs 28.8 kPa (P = .002), respectively. CONCLUSIONS: Our results indicate that SWE may be useful in differentiating patients with advanced cirrhosis from those with fibrosis and may be helpful in the noninvasive diagnosis and monitoring of HCV recurrence after LTX.

Hepatocellular Carcinoma Is a Negative Predictor of Sustained Viral Response in Liver Transplant Recipients With Hepatitis C Treated With Direct-Acting Antivirals.

INTRODUCTION: Treatment with direct-acting antivirals (DAA) for hepatitis C (HCV) in liver transplant (LTX) recipients is very effective, but some studies showed that the treatment effectiveness might be impaired in patients with hepatocellular carcinoma (HCC). The study aimed to evaluate the predictors of DAA treatment failure in LTX recipients. METHODS: Liver biopsy was done before the treatment in 107 of the 120 patients included. All patients had an abdominal ultrasound and liver elastography performed before and after the therapy. Blood HCV polymerase chain reaction was done before; during; and at 4, 12, and 24 weeks after the treatment. RESULTS: Overall sustained viral response 24 weeks after treatment (SVR24) was 96%. There were 2 patients with HCC at the start of the DAA treatment and 3 cases of HCC recurrence during a 1-year follow-up. Treatment failure was observed in 1/115 (0.9%) patients without HCC and 4/5 (80%) with active HCC (P = .0001). Liver fibrosis and previous interferon treatment had no impact on treatment efficacy. Time to viremia elimination on treatment was shorter in the responder versus nonresponder group (28 vs 58 days, P = .03). CONCLUSIONS: HCC is a negative predictor of DAA therapy success in LTX recipients.

Long-Term Follow-up of Liver Transplant Recipients Treated With Direct-Acting Antiviral Agents for Hepatitis C Recurrence After Transplantation.

BACKGROUND: Treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LTX) with direct-acting antiviral agents (DAA) is effective and leads to sustained viral response (SVR) in most cases. Long-term effect of HCV elimination on LTX function is not clear. The aim of the study was to evaluate the long-term influence of DAA with HCV on the liver function in LTX recipients. METHODS: The study included 120 LTX patients with HCV recurrence. Before starting DAA therapy, all patients underwent liver biopsy and elastography. Biochemical tests and HCV viremia were assessed at baseline, 4, 12, and 24 weeks and 24 months after the end of treatment (EOT). The study protocol conformed with the Declaration of Helsinki. RESULTS: In the HCV genotype 1 (G1) group, 106 patients were treated with ledipasvir/sofosbuvir with ribavirin (RBV), and 3 patients received paritaprevir/ritonavir/ombitasvir/dasabuvir/RBV. All HCV genotype 3 (G3) patients were treated with sofosbuvir/RBV; all HCV genotype 4 (G4) patients were treated with paritaprevir/ombitasvir/RBV. The efficacy of the treatment defined as SVR at week 12 after EOT (SVR12) was 97.3% in G1 group, 75% in G3, and 100% in G4 group. Median alanine (ALT) and aspartate (AST) transaminase before therapy were 44.0 IU/mL and 42.5 IU/mL, respectively. Median ALT and AST at 24 months after EOT were 17 IU/mL and 22 IU/mL, respectively. The lack of transaminases normalization was observed in 10 patients 24 months after EOT. CONCLUSION: The efficacy of DAA therapy of HCV recurrence after LTX is as high as that reported in randomized clinical trials. It is also associated with the improvement of liver function tests during long-term follow-up.

Efficacy, safety, and pharmacokinetics of simeprevir, daclatasvir, and ribavirin in patients with recurrent hepatitis C virus genotype 1b infection after orthotopic liver transplantation: The Phase II SATURN study.

BACKGROUND: Recurrent hepatitis C virus (HCV) infection following liver transplantation is associated with accelerated progression to graft failure and reduced patient survival. METHODS: The Phase II, open-label SATURN study (NCT01938625) investigated the combination of simeprevir (SMV), daclatasvir (DCV), and ribavirin (RBV) administered for 24 weeks in 35 patients with recurrent HCV genotype (GT) 1b infection after orthotopic liver transplantation (OLT). RESULTS: High rates of both on-treatment and sustained virologic response 12 weeks after end of treatment (SVR12) were achieved in patients who were either treatment-naïve or had failed post-OLT treatment with peginterferon and RBV. Overall, 91% of patients (32/35) achieved SVR12. The combination was generally well tolerated, with an adverse event profile consistent with that observed in previous clinical trials of SMV or DCV separately. Co-administration of SMV with cyclosporine resulted in significantly increased SMV plasma exposures, which was not the case with the co-administration of SMV with tacrolimus. Therefore, the concomitant use of SMV with cyclosporine is not recommended. CONCLUSION: The interferon-free combination of SMV, DCV, and RBV administered for 24 weeks was shown to be effective and well tolerated in the treatment of post-OLT HCV GT1b-infected patients.

Improvement of graft function following Roux-en-Y gastric bypass surgery in a morbidly obese kidney recipient: a case report and literature review.

BACKGROUND: Transplantation is the best and approved method of renal replacement therapy. Graft function depends not only on proper regulation of immune processes but also on the optimal control of chronic diseases. The obesity epidemic involves the healthy population and organ recipients equally. Obesity and metabolic syndrome lead to a number of disorders exerting adverse effects on the transplanted organ. CASE REPORT: We report a case of a kidney recipient, 12 years after transplantation, with chronic graft failure (serum creatinine level 2.1 mg/dl, GFR 31 ml/min/1.73 m(2)), morbid obesity (weight 139.8 kg, BMI 46.2 kg/m(2), excess body mass 73.1 kg), hypertension, poorly controlled type 1 diabetes (HbA1c 8.8%), and ischemic heart disease. The cause of chronic kidney disease was diabetic nephropathy. The patient was the first Polish kidney recipient referred for bariatric gastric bypass surgery (GB). Directly after surgery, transient creatinine elevation (4.7 mg/dl) was noted. There was no reduction in diuresis. Desired weight loss was achieved within 12 months after surgery (body mass 81.9, BMI 27.1 kg/m(2), percentage loss of excess weight 86.9%) with improved graft function (serum creatinine level 1.3 mg/dl, GFR 45.1 ml/min/1.73 m(2)) and reduction of daily insulin requirement from 74 to 40 units. The severity of hypertension and ischemic heart disease diminished as well. CONCLUSIONS: Metabolic surgery is the best treatment of obesity and may contribute to post-transplantation care if weight gain is observed, as a result of the interaction of many factors leading to deterioration of renal graft function.

Liver transplantation for HCV cirrhosis; cautious optimism after 10 years of experience.

BACKGROUND: Currently, HCV (hepatitis C virus) cirrhosis is one of the most common indications for liver transplantation (LTx) in Europe and North America among adults. Very early after LTx, histological examinations of liver biopsies in a group of HCV-positive recipients show important differences compared to other indications for transplantation. MATERIAL/METHODS: We described results of 121 primary LTx for HCV cirrhosis. HCV-RNA PCR was positive in 94% of primary graft recipients prior to LTx. Co-existing HCC was diagnosed in 20.66% of recipients. RESULTS: One-year, 5-year, and 10-year survivals in the HCV-positive recipient group were 87.6%, 85.9%, and 84.3%, respectively. Symptomatic recurrent hepatitis was diagnosed in 58/121 (47.54%) recipients, and 41.3% presented with recurrence within the first 6 months. None of the PCR-negative recipients developed recurrent hepatitis prior to LTx. The rescue therapy for recurrent HCV hepatitis consist of Interferon and Ribavirin; the sustained virologic response (SVR) was obtained in 50% and 41% of recipients at 24 and 48 weeks, respectively, after treatment cessation. CONCLUSIONS: Despite almost universal recurrence of HCV after LTx, results of transplantation are relatively good. Modification of immunosuppression, younger organ selection, and avoiding steroid pulses for rejection improve the results. Inclusion of combination therapy with interferon and Ribavirin allows for more than 40% SVR.

Safety and efficacy of high dose ATG bolus administration on rewascularization in kidney graft patients--long term results.

BACKGROUND: Various preparations of ALG/ATG have been used in clinical transplantation for more than 30 years. In recent years the number of high immunological risk patients has increased and biological agents are being used as induction therapy. The aim of this prospective, randomized study was to asses the safety and efficacy of a single high dose of antithymocyte globulin (9 mg/kg ATG Fresenius S) in cadaveric renal transplantation. The maintenance immunosuppressive regimen consisted of steroids, mycophenolate mofetil (converted after the fourth month to azathioprine), and cyclosporine. MATERIAL/METHODS: Between November 1997 and April 1999, 79 recipients were included into the study. Patients were randomized to ATG (n=40) or the standard treatment group (n=39) with a follow up period of 5 years. RESULTS: The incidence of acute rejection was lower in the ATG group--9 patients (22.5%) compared to 14 in the control group (35.9%) (p=NS). The total number of all acute rejections episodes in the ATG group was 11 and 23 in the control group. Steroid resistant rejections occurred in 4 (10%) and 8 (20.5%) patients respectively. The number of infectious complications was similar in both groups (65% - ATG, 67.5% - control, p=NS). Graft survival was 70% for the ATG and 69.23% for the control group. Death censored graft survival was 85% in the ATG and 74.43% in the control group (p=NS). CONCLUSIONS: Induction Therapy with high single dose of ATG seems to be safe and efficacious in kidney transplantation.

[Cytokines and growth factors serum level and renal allograft function (preliminary report)]. / Cytokiny i czynniki wzrostu w surowicy u biorców nerki allogenicznej a losy przeszczepu (doniesienie wstepne).

Long-term cyclosporine nephrotoxicity, subclinical rejections are risk factors of chronic allograft nephropathy. In a prospective, randomized study 44 pts. were randomized either to a reduced dose of CyA and daclizumab (group A, n = 22) or to a normal dose of CyA without daclizumab (group B, n = 22). Both groups were treated with MMF and prednisone. Number of rejection episodes was the primary endpoint. The secondary endpoints were renal function; histological parameters related to CyA; serum level of TGF-beta, PDGF-BB, blockade of CD25 molecule and surface expression of CD3, CD4, CD8, CD69, CD11a, CD49d, CD28, CD152 molecules in the subpopulations of T cells in the peripheral blood. A low incidence of clinically suspected rejection episodes were observed (19% in group A and 12.4% in group B; NS). The protocol biopsies at 3 month emerged 7 subclinical rejection episodes (4 in group A and 3 in group B). Serum creatinine level did not differ between examined groups. Chronic histopathologic changes related to CyA progressed significantly at the 3 month biopsies in both groups (with no differences between groups). Serum TGF-beta, PDGF did not differ between groups. Expression of CD25, CD152 molecule was significantly lower in group A than in group B. Immunosuppression regiment with low CyA dose with daclizumab, MMF, prednisone seems to be efficient and safe in low-risk rejection kidney allograft recipients.

[Complement split product C4 as the indicator of immunological activity in chronic allograft rejection]. / Czasteczka rozpadu dopelniacza C4d jako wyznacznik aktywnosci immunologicznej procesu przewleklego odrzucania przeszczepu nerkowego.

The patients after renal transplantation with deteriorating graft function were included to the study. The aim of the study was to establish the usefulness of stabile complement split product C4d expression as the independent indicator of immunological activity in chronic rejection. The C4d expression was studied on fresh frozen tissue with immunofluorescence method. The intensification of immunosuppression regimen was also introduced and azathioprine was exchanged with mycofenolate mofetil. The protocol biopsies a year after inclusion are planned to be done. In our study there was positive correlation between C4d expression and previous acute rejection episodes, morphological changes specific for chronic rejection and clinical improvement after immunosuppression enhancement.

[The usefulness of tubular and glomerular proteinuria measurement in non-invasive diagnosis of vascular changes accompanying chronic allograft nephropathy]. / Ocena przydatnosci oznaczania bialek wydalanych z moczem w rozpoznawaniu stopnia zaawansowania zmian naczyniowych towarzyszacych przewleklej nefropatii alloprzeszczepu nerkowego.

Chronic allograft nephropathy (CAN) is the most important cause of late renal allograft loss. The standard diagnosis of CAN is based on pathological examinations according to Banff'97 scheme. The aim of the study was to evaluate the usefulness of tubular and glomerular proteinuria in non-invasive recognition of vascular changes accompanying CAN (AH--arteriolar hyaline thickening, CV--vascular fibrous intimal thickening). beta 2- and alpha 2-microglobulin (beta 2-m and alpha 2-m), albumin (alb), immunoglobulin G (IgG), total protein (tp) and creatinine (cr) concentration were measured in the second time urine specimen in 66 renal allograft recipients. Then the subsequent renal biopsies were done. The aim of statistical analysis (MANOVA, Stepwise Discriminant Analysis, SDA) was to diagnose CV and AH changes based on results of urine analysis listed above and the patient's age, time after transplantation and serum creatinine level (scr). Results obtained with statistical analysis were in 90.91% and 87.69% identical with CV and AH pathological diagnoses, respectively.