Liver transplant from Anti‐HBc‐positive,HBsAg‐negative donor into HBsAg‐negative recipient: is it safe? A systematic review of the literature

Avelino‐Silva VI, D′Albuquerque LAC, Bonazzi PR, Song ATW, Miraglia JL, de Brito Neves A, Abdala E. Liver transplant from Anti‐HBc‐positive, HBsAg‐negative donor into HBsAg‐negative recipient: is it safe? A systematic review of the literature.
Clin Transplant 2010: 24: 735–746. © 2010 John Wiley & Sons A/S. Abstract: Introduction: After liver transplant (LT) from Anti‐HBc+/HBsAg? donors into HBsAg? recipients, transmission of hepatitis B virus (HBV) may occur (de novo HBV infection). This study analyzes the incidence of de novo HBV infection in HBsAg? recipients of Anti‐HBc+/HBsAg? LT with respect to: (i) the recipients’ HBV serology and (ii) the type of preventive therapy adopted. Methods: A systematic review of the literature using the electronic database Medline. Results: Five hundred and fifty‐two LT in 36 articles were selected. Lamivudine, Hepatitis B immune globulin (HBIG), revaccination, and combined therapies were employed in multiple strategies as preventive interventions. Naïve recipients had a high risk of de novo HBV infection, with smaller incidences when HBIG and lamivudine were used, either alone or in association. Vaccinated recipients or those with isolated hepatitis B core antibodies (Anti‐HBc) and previous HBV infection had lower risks of viral transmission, additionally reduced by any prophylaxis adoption. Discussion: LT from Anti‐HBc+/HBsAg? donors into HBsAg? recipients is apparently safe, as long as the recipient is vaccinated or presents an isolated Anti‐HBc or previous HBV infection and some prophylaxis is employed. Currently lamivudine seems the best alternative; other nucleoside analogs and revaccination strategies should be considered in future studies. Follow‐up and preventive therapies should be maintained for five yr or preferably throughout the recipients’ life span.     

Preemptive living donor kidney transplantation: do the benefits extend to all recipients?

BACKGROUND: Preemptive kidney transplantation (prior to the institution of dialysis) avoids the morbidity and mortality of dialysis; however, detailed studies of high-risk patients are lacking. The aim of the current study was to compare recent outcomes of preemptive (P) versus nonpreemptive (NP) living donor kidney transplantation with an emphasis on high-risk recipients. METHODS: We retrospectively analyzed 438 sequential solitary living donor kidney transplants at our institution between January 2000 and December 2002. In all, 44% were preemptive. NP recipients were dialyzed for 21+/-36 months (range 1-312 months). RESULTS: Overall, three-year patient survival was similar in the NP and P groups. When stratified by diabetes and age >65 years, P and NP recipients again showed similar survival. Death-censored three-year graft survival was better in the P group (97% vs. 90%, P=0.01), but was not significant by multivariate analysis. Delayed graft function was more frequent in NP vs. P (10% vs. 4%; P=0.01), but other early complications were similar including: acute rejection, 16% vs. 11% (P=0.11); primary nonfunction, 3% vs. 2% (P=0.38); and wound complications, 19% vs. 17% (P=0.54). Glomerular filtration rate at three years was similar in the two groups (53+/-23 preemptive vs. 52+/-20 ml/min nonpreemptive; P=0.37). CONCLUSION: With prompt referral and workup, preemptive kidney transplantation can be performed successfully in a large percentage of renal allograft recipients. Preemptive transplantation avoids unnecessary dialysis and should be emphasized as initial therapy for many patients with end-stage renal disease.     

Parathyroid resistance to FGF23 in kidney transplant recipients: back to the past or ahead to the future?

Fibroblast growth factor 23 (FGF23) modulates the metabolism of minerals and vitamin D. In chronic kidney disease (CKD), this process is disturbed owing to decreased parathyroid expression of FGF23's receptor complex Klotho-FGF receptor 1. In this issue, Krajisnik and colleagues demonstrate that similar alterations occur in parathyroid glands from kidney transplant recipients in association with a decline in allograft function. Is it possible that these data can be extrapolated to general early-stage CKD patients?     

Does timing of post‐renal transplant diuresis affect graft survival in live‐donor renal transplants?

Study Type – Prognosis (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Delayed graft function had an adverse impact upon graft survival in deceased kidney transplantation. The current study provides evidence of a similar effect in an exclusive live donor renal recipient population.

OBJECTIVE

To study the effect of timing of diuresis on short and long term graft survival in live‐donor (LD) renal transplants.

METHODS

Between 1976 and 2005, 1747 consecutive LD renal transplants were performed in a single institution. Patients were classified according to timing of diuresis after vascular de‐clamping; group 1 included patients with diuresis within 10 min; group 2 started diuresis between 10 and 60 min after de‐clamping; group 3 started diuresis between 1 and 24 h after de‐clamping; and group 4 started diuresis >24 h after de‐clamping. Patients’ data were stored on an electronic database and were reviewed for risk factors and clinical relevance of timing of diuresis.

RESULTS

Groups 1–4 comprised 1598 (91.5%), 87 (5%), 44 (2.5%) and 18 (1%) patients, respectively. By multivariate analysis, vascular thrombosis was the significant risk factor for delayed diuresis. Delayed diuresis was significantly associated with the occurrence of acute tubular necrosis (ATN), and acute and chronic rejection. Graft and patient survival rates were significantly affected by the timing of diuresis. The 1‐year graft survival rates were 93.8, 83.0, 83.6 and 55.6%, and the 5‐year graft survival rates were 77.4, 59.4, 69.4 and 35.7% in groups 1, 2, 3 and 4, respectively (P < 0.001). The 1‐year patient survival rates were 96.5, 84.4, 90.7 and 61.1% and the 5‐year patient survival rates were 87.1, 72.0, 78.1 and 52.4% in groups 1, 2, 3 and 4, respectively (P < 0.001).

CONCLUSION

Delayed diuresis is a rare event after LD renal transplantation, which has an adverse effect on short‐ and long‐term graft and patient survival.     

Is pre‐transplant sensitization against angiotensin II type 1 receptor still a risk factor of graft and patient outcome in kidney transplantation in the anti‐HLA Luminex era? A retrospective study

We aimed to assess the correlation of anti‐angiotensin II type 1 receptor antibodies (anti‐AT1R‐Abs) before transplantation on a multicentric cohort of kidney transplant recipients (2008–2012), under tacrolimus and mycophenolate mofetil (MMF), screened by Luminex technology for anti‐HLA immunization. Anti‐AT1R antibody levels were measured by ELISA in pretransplantation sera of 940 kidney recipients from three French centers of the DIVAT cohort. Multivariable Cox models estimated the association between pretransplant anti‐angiotensin II type 1 receptor antibodies and time to acute rejection episodes (ARE) or time to graft failure. Within our cohort, 387 patients (41.2%) had pretransplant AT1R‐Abs higher than 10 U/ml and only 8% (72/970) greater than 17 U/ml. The cumulative probability of clinically relevant (cr)‐ARE was 22.5% at 1 year post‐transplantation [95% CI (19.9–25.4%)]. The cumulative probability of graft failure and patient death were 10.6% [95% CI (8.4–13.3%)] and 5.7% [95% CI (4.0–8.1%)] at 3 years post‐transplantation, respectively. Multivariate Cox models indicated that pretransplant anti‐AT1R antibody levels higher than 10 U/ml were not significantly independently associated with higher risks of acute rejection episodes [HR = 1.04, 95% CI (0.80–1.35)] nor with risk of graft failure [HR = 0.86, 95% CI (0.56–1.33)]. Our study did not confirm an association between pretransplant anti‐AT1R antibody levels and kidney transplant outcomes.     

Beyond survival: how well do transplanted livers work? A preliminary comparison of standard‐risk,high‐risk,and living donor recipients

To help decrease mortality on the liver transplant waitlist, transplant centers are using living donors (LD) and high‐risk donors (HRD) in addition to standard‐risk donors (SRD). HRD is defined as having a donor risk index score higher than 1.6, which suggests a great risk of graft failure. Recent studies have examined survival rates between HRD and SRD recipients; however, little is known about outcomes other than survival, specifically psychosocial outcomes. The purpose of this preliminary, prospective study was to compare post‐transplant psychosocial and recovery outcomes between SRD and LD and HRD liver recipients. These outcomes include cognitive functioning, psychological distress, quality of life, and self‐reported and objective measures of recovery. Eighty‐four patients provided baseline and six‐month post‐transplant data. There were generally no statistically significant differences at baseline or the six‐month follow‐up, suggesting that patients receiving HRD livers have similar outcomes to those who receive SRD livers. However, some effect sizes suggest potential advantages for LD recipients compared to SRD recipients. Transplant centers may be more willing to encourage patients to accept HRD or LD livers knowing that they may have comparable outcomes to SRD recipients, which also has implications for the transplant waitlist.     

Early post‐liver transplant surgical morbidity in HIV‐infected recipients: risk factor for overall survival? A nationwide retrospective study

The aim of the study was to analyse the risk factors for early surgical complications requiring relaparotomy and the related impact on overall survival (OS) in HIV‐infected patients submitted to liver transplantation. Thus a retrospective investigation was conducted on a nationwide multicentre cohort of 157 HIV patients submitted to liver transplantation in six Italian Transplant Units between 2004 and 2014. An early relaparotomy was performed in 24.8% of cases and the underlying clinical causes were biliary leak (8.2%), bleeding (8.2%), intestinal perforation (4.5%) and suspect of vascular complications(3.8%). No differences in terms of prevalence for either overall or cause‐specific early relaparotomies were noted when compared with a non‐HIV control group, matched for MELD, recipient age, HCV‐RNA positivity and HBV prevalence. While in the control group an early relaparotomy appeared a negative prognostic factor, such impact on OS was not noted in HIV recipients. Nonetheless increasing number of relaparotomies were associated with decreased survival. In multivariate analysis, preoperative refractory ascites and Roux‐en‐Y choledochojejunostomy reconstruction were significant risk factors for early relaparotomy. To conclude, in HIV liver transplanted patients, an increasing number of early relaparotomies because of surgical complications does negatively affect the OS. Preoperative refractory ascites reflecting a severe portal hypertension and a difficult biliary tract reconstruction requiring a Roux‐en‐Y choledochojejunostomy are associated with increased risk of early relaparotomy.     

Visceral Leishmaniasis in renal transplant recipients: is it still a challenge to the nephrologist?

A case of visceral Leishmaniasis in a renal transplant recipient is reported because of its peculiar clinical presentation: the presence of most clinical signs of the disease, such as high-grade fever, marked leucopenia, and splenomegaly, but persistent negativity of serology and of bone marrow smear. Forty days after the first bone marrow biopsy, the diagnosis was made possible by a second biopsy, and the treatment was started with antimonial compounds, which led to complete remission of symptoms. A relapse was observed 1 month after discontinuation of therapy, successfully treated with a new cycle of the same drug and allopurinol. The diagnosis of Leishmaniasis must always be considered in immunosuppressed transplant recipients with fever and leucopenia of unknown origin, even when serology and bone marrow smear are negative.     

Small dense low-density lipoprotein in renal transplant recipients: a potential target for prevention of cardiovascular complications?

BACKGROUND: Immunosuppressive therapy is frequently associated with dyslipidemia, which is involved in cardiovascular morbidity and mortality in transplant patients. Beyond classical factors, such as low-density lipoprotein (LDL) cholesterol (LDL-C), qualitative abnormalities of lipoproteins, such as presence of the atherogenic factor, small dense LDL, may be of interest for a cardiovascular risk assessment. This study was designed to explore LDL size in renal transplant recipients in relation to quantitative lipid parameters and apolipoprotein (apo) CIII polymorphism. METHODS: Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), LDL-C, apoA1, apoB, apoCIII, and LDL size were measured in 62 patients of mean age 45 +/- 13 years including 71% men at 2 +/- 0.5 years after renal transplantation. Thirty-two patients received cyclosporine (CsA), while 30 received tacrolimus (FK). ApoCIII Sstl genotype was determined by restriction fragment length polymorphism. RESULTS: The CsA group exhibited higher TC (P = .001), LDL-C (P = .004), non-HDL-C (P = .009), HDL-C (P = .03), apoB (P = .008), and apoCIII (P = .002) levels than the FK group. However, LDL-C (CsA: 3.7 +/- 1.2, FK: 3.0 +/- 0.6 mmol/L) and triglyceride levels (CsA: 1.55 mmol/L, FK: 1.37 mmol/L) were near the normal range in both groups. Allelic frequency of the sparse A2 allele associated with hypertriglyceridemia was 6%, similar to the general population. LDL size, which was comparable in the CsA and FK groups (25.87 +/- 0.89 vs 25.75 +/- 0.62 nm, respectively), inversely correlated with TG/HDL ratio (P = 10(-4)). Prevalence of small dense LDL (defined as <25.5 nm) was 26% in the CsA group and 33% in the FK group. CONCLUSION: After LDL-C goal has been achieved, LDL size modulation may be taken into account in order to prevent cardiovascular complications.