Steroid‐free living donor liver transplantation in adults: impact on hepatitis C recurrence

Abstract: Introduction: Although steroid‐free immunosuppression has been proven to be safe and feasible for liver transplantation, its impact on hepatitis C virus (HCV) recurrence remains unknown. We aimed to clarify the impact of steroid‐free immunosuppression on post‐operative HCV recurrence after living donor liver transplantation (LDLT). Patients and methods: Of 32 adult patients with HCV cirrhosis who underwent LDLT between 1999 and 2007 at our hospital, 28 were enrolled in this prospective study. We used steroid‐free immunosuppression, consisting of a calcineurin inhibitor, mycophenolate mofetil and anti‐CD25 antibody in 18 patients (F‐group), and the remaining 10 patients received steroid‐based immunosuppression (S‐group) during the same period. Results: Patient characteristics were similar between the two groups. Steroid‐free immunosuppression was associated with lower incidence of CMV infection (p = 0.049) and higher incidence of instituting preemptive anti‐HCV therapy (p = 0.015) without increasing acute cellular rejection in the F‐group than that in the S‐group. In the early period after LDLT, the serum HCV‐RNA level remained suppressed in the F‐group, whereas it increased rapidly in the S‐group (p < 0.05). HCV recurrence was less frequent in the F‐group (18.1% at one yr) than in the S‐group (46.0%) (p = 0.009). Conclusions: Steroid‐free immunosuppression was confirmed to be safe and feasible for HCV‐positive recipients in LDLT, and was associated with suppressed HCV replication and HCV recurrence after LDLT.     

Incidence,risk factors,and outcomes of stroke post‐transplantation in patients receiving a steroid sparing immunosuppression protocol

Corticosteroid use after transplantation is associated with an increased incidence of cardiovascular events and death. Cerebrovascular disease is a common cause of morbidity and mortality post‐renal transplantation; however, a dedicated analysis of cerebrovascular disease in recipients of a steroid sparing protocol has not been reported. The aim of this study was to examine the incidence, risk factors, and outcomes of CVA in transplant recipients receiving a steroid sparing protocol. We retrospectively analyzed 1237 patients who received a kidney alone or a simultaneous pancreas and kidney (SPK) transplant. Fifty‐six of 1237 (4.53%) patients had a CVA post‐transplant. All‐cause mortality was significantly higher in the CVA group compared with the non‐CVA group, OR: 3.4 (1.7–7.0), p < 0.001. Factors found to be associated with increased risk of CVA by multivariate analysis were older age, HR: 1.07 (1.04–1.09), p < 0.001; diabetes at the time of transplantation, HR: 2.83 (1.42–5.64), p = 0.003; corticosteroid use pre‐transplant, HR: 3.27 (1.29–8.27), p = 0.013 and recipients of a SPK, HR: 4.03 (1.85–8.79), p < 0.001. This study has identified subgroups of patients who are at increased risk of CVA post‐transplant in patients otherwise receiving a steroid sparing immunosuppression protocol.     

Live donor liver transplantation with older donors: Increased long‐term graft loss due to HCV recurrence

Using our prospectively collected database all adult hepatitis C virus (HCV)‐positive patients receiving an adult‐to‐adult LDLT between October 2000 and May 2014 were identified. Outcome of LDLT with grafts from younger (<50 years=128) vs older donors (≥50 years=31) was compared. Post‐transplant graft function, postoperative complications and incidence of HCV recurrence were evaluated. Long‐term graft and patient survival was calculated. No difference in graft function was observed between younger and older grafts. Overall complications were similar between both groups. The severity of complications determined by the Dindo‐Clavien score was similar. Graft loss from HCV recurrence was significantly less frequent in younger grafts (18% vs 62%, P = 0.001). Young vs older livers had a trend toward improved 1‐, 5‐, and 10‐year graft survival (89% vs 87%, 77% vs 69%, 70% vs 55%, P = 0.096), while patient survival was comparable between both groups (91% vs 90%, 78% vs 69%, 71% vs 60%, P = 0.25). In conclusion, LDLT with older vs younger grafts are more frequently associated with long‐term graft loss due to HCV recurrence. Differences in graft survival might be more prominent with prolonged (≥5‐year) follow‐up. Living donor‐recipient matching is particularly important for younger HCV‐positive recipients.     

Incidence and risk factors for new‐onset diabetes in living‐donor liver transplant recipients

With the increased number of long‐term survivors after liver transplantation, new‐onset diabetes after transplantation (NODAT) is becoming more significant in patient follow‐up. However, the incidence of new‐onset diabetes after living‐donor liver transplantation (LDLT) has not been well elucidated. The aim of this study was to evaluate the incidence and risk factors for NODAT in adult LDLT recipients at a single center in Japan. A retrospective study was performed on 161 adult patients without diabetes who had been followed up for ≥three months after LDLT. NODAT was defined according to the 2003 American Diabetes Association/World Health Organization guidelines. The recipient‐, donor‐, operation‐, and immunosuppression‐associated risk factors for NODAT were assessed. Overall, the incidence of NODAT was 13.7% (22/161) with a mean follow‐up of 49.8 months. In a multivariate analysis, the identified risk factors for NODAT were donor liver‐to‐spleen (L‐S) ratio (hazard ratio [HR] = 0.022, 95% confidence interval [CI] = 0.001–0.500, p = 0.017), and steroid pulse therapy for acute rejection (HR = 3.320, 95% CI = 1.365–8.075, p = 0.008). In conclusion, donor L‐S ratio and steroid pulse therapy for acute rejection were independent predictors for NODAT in LDLT recipients. These findings can help in screening for NODAT and applying early interventions.     

Simplified one‐orifice venoplasty for middle hepatic vein reconstruction in adult living donor liver transplantation using right lobe grafts

Middle hepatic vein (MHV) reconstruction is often essential to avoid hepatic congestion and serious graft dysfunction in living donor liver transplantation (LDLT). The aim of this report was to introduce evolution of our MHV reconstruction technique and excellent outcomes of simplified one‐orifice venoplasty. We compared clinical outcomes with two reconstruction techniques through retrospective review of 95 recipients who underwent LDLT using right lobe grafts at our institution from January 2008 to April 2012; group 1 received separate outflow reconstruction and group 2 received new one‐orifice technique. The early patency rates of MHV in group 2 were higher than those in group 1; 98.4% vs. 88.2% on postoperative day 7 (p = 0.054) and 96.7% vs. 82.4% on postoperative day 14, respectively (p = 0.023). Right hepatic vein (RHV) stenosis developed in three cases in group 1, but no RHV stenosis developed because we adopted one‐orifice technique (p = 0.043). The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in group 2 were significantly lower than those in group 1 during the early post‐transplant period. In conclusion, our simplified one‐orifice venoplasty technique could secure venous outflow and improve graft function during right lobe LDLT.     

Interactions between virus‐related factors and post‐transplant ascites in patients with hepatitis C and no cirrhosis: role of cryoglobulinemia

Refractory ascites may appear in liver transplant recipients with recurrence of hepatitis C virus infection, even in the absence of advanced fibrosis. The mechanisms are unclear. The aim was to determine whether post‐transplant cryoglobulinemia could be a predisposing factor for ascites in this population. Retrospective data of 82 liver transplant recipients with HCV recurrence surviving more than 1 year were collected. Cryoglobulinemia was systematically tested after transplantation. All patients had 1‐year protocol biopsy with assessment of sinusoidal distension, perisinusoidal fibrosis, and centrolobular necrosis. Additional biopsies were performed when needed. Fourteen of 82 patients (17%) developed refractory ascites. When ascites appeared, fibrosis was stage F0–F1 in 36% and F2–F3 in 57%. Factors independently associated with post‐transplant ascites were pretransplant refractory ascites (P = 0.001), fibrosis ≥stage 2 at 1 year (P = 0.002), perisinusoidal fibrosis at 1 year (P = 0.02), and positive cryoglobulinemia (P = 0.02). Patients with ascites had a significantly worse prognosis compared to those without ascites. Refractory ascites may occur in liver transplant recipients with HCV recurrence in the absence of advanced fibrosis. The finding that both positive cryoglobulinemia and perisinusoidal fibrosis at 1 year were significantly associated with ascites suggests that liver microangiopathy is involved in the mechanisms of HCV‐related ascites.     

Comparing 10‐yr renal outcomes in deceased donor and living donor liver transplants

Few studies have explored whether the type of LT, deceased donor LT (DDLT) or living donor LT (LDLT), impacts long‐term renal outcomes. We performed a retrospective analysis of 220 LT recipients at our institution to study their renal outcomes at 10 yr. Exclusion criteria were age ≤ 18 yr, graft survival ≤6 months, and multiorgan transplants; 108 DDLTs and 62 LDLTs were eligible. At baseline, DDLTs had a lower eGFR than LDLTs and 10.2% of DDLTs were on dialysis as compared to 0% of LDLTs. At 10 yr, seven DDLT and three LDLT recipients required dialysis or renal transplant (p = 0.75). In recipients with graft survival >6 months, DDLTs had a slower decline in eGFR as compared to LDLTs (p < 0.01). Among LDLTs, the decline in eGFR continued over the entire 10‐yr period, whereas among DDLTs, the decline in eGFR slowed significantly after six months (p = 0.01). This difference between the two groups was not seen among patients in the highest quartile of baseline eGFR. Patient survival and graft survival were similar. In conclusion, the incidence of end‐stage renal disease was similar in both DDLT and LDLT patients, but LDLT recipients seem to have a more sustained decline in eGFR when compared with DDLT recipients.     

Clinical analysis of recurrent hepatocellular carcinoma after living donor liver transplantation

This study aimed to analyze the clinical outcomes and factors influencing the outcome in the recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT). Between October, 1997 and September, 2010, 25 (16.0%) of 156 patients who had undergone LDLT for HCC experienced recurrence. All patients with recurrence, with a single exception, were in the high‐risk group. Among patients with recurrence, 76.0% of patients experienced recurrence within one yr after LDLT. One‐ and five‐yr survival rates of recurred patients were 56.0% and 8.6%, respectively. Among them, 32% of patients were treated with curative‐intent treatment, and their one‐ and five‐yr survival rates were 62.5% and 25.0%, respectively. Beyond the Milan criteria at liver transplantation (LT) (p = 0.032), multiple recurrence (p = 0.001), and palliative treatment for recurrent tumors (p = 0.049) were related to poor survival after recurrence. Additionally, the independent prognostic factors included multiple recurrence (p = 0.005) and the Milan criteria at LT (p = 0.047). Because almost all recurrent cases belonged to the high‐risk group and recurred within two yr, the high‐risk group should undergo close follow‐up for early detection and be treated with liver‐directed therapies. Although the prognosis of recurrent HCC after LDLT is poor, long‐term survival can be expected on a single recurrence and curative treatment.     

The risk of recurrent IgA nephropathy in a steroid‐free protocol and other modifying immunosuppression

Recurrent glomerulonephritis is an important cause of kidney allograft failure. The effect of immunosuppression on recurrent IgA nephropathy (IgAN) is unclear. We analyzed the impact of steroids and other immunosuppression on the risk of recurrent IgAN post‐kidney transplantation. Between June 1989 and November 2008, 3311 kidney transplants were performed at our center. IgAN was the primary disease in 124 patients; of these, 75 (60.5%) patients received steroid‐based immunosuppression (15 undergoing late steroid withdrawal), and 49 (39.5%) were maintained on steroid‐free immunosuppression. Recurrent IgAN was diagnosed in 27 of 124 (22%) patients in clinically indicated kidney allograft biopsies over a median follow‐up of 6.86 ± 5.4 yr. On cox proportional hazards model multivariate analysis, the hazard risk (HR) of IgAN recurrence was significantly higher in patients managed with steroid‐free (HR 8.59: 3.03, 24.38, p < 0.001) and sirolimus‐based (HR = 3.00:1.16, 7.75, p = 0.024) immunosuppression without antilymphocyte globulin induction (HR = 4.5: 1.77, 11.73, p = 0.002). Mycophenolate use was associated with a lower risk (HR = 0.42: 0.19, 0.95, p = 0.036), whereas cyclosporine did not have a significant impact on the risk of IgAN recurrence (p = 0.61). These results warrant future prospective studies regarding the role of steroids and other immunosuppression drugs in reducing recurrence of IgAN and other glomerulonephritis post‐transplant.     

Longitudinal growth on an everolimus‐ versus an MMF‐based steroid‐free immunosuppressive regimen in paediatric renal transplant recipients

Concerns have been raised that mammalian target of rapamycin inhibitors in pediatric transplant recipients might interfere with longitudinal bone growth by inhibition of growth factor signaling and growth plate chondrocyte proliferation. We therefore undertook a prospective nested, case‐control study on longitudinal growth over 2 years in steroid‐free pediatric renal transplant recipients. Fourteen patients on a steroid‐free maintenance immunosuppressive regimen consisting of low‐dose everolimus (EVR) in conjunction with low‐dose cyclosporine (CsA) were compared to a matched cohort of 14 steroid‐free patients on a standard dose mycophenolate mofetil (MMF) regimen in conjunction with a standard dose calcineurin inhibitor (CNI). The mean change in height standard deviation (SD) score in the first study year was 0.31 ± 0.71 SD score in the EVR group compared to 0.31 ± 0.64 SD score in the MMF group (P = 0.20). For the entire study period of 2 years, the change in height SD score in the EVR group was 0.43 ± 0.81 SDS compared to 0.75 ± 0.85 SDS in the MMF group (P = 0.32). The percentage of prepubertal patients experiencing catch‐up growth, defined as an increase in height SD score ≥0.5 in 2 years, was similar in the EVR group (5/8, 65%) and the MMF group (6/8, 75%; P = 1.00). Longitudinal growth over 2 years in steroid‐free pediatric patients on low‐dose EVR and CsA is not different to that of a matched steroid‐free control group on an immunosuppressive regimen with standard‐dose CNI and MMF. Hence, low‐dose EVR does not appear to negatively impact short‐term growth in pediatric renal transplant recipients.     

Comparison of alemtuzumab vs. antithymocyte globulin induction therapy in primary non‐sensitized renal transplant patients treated with rapid steroid withdrawal

Alemtuzumab and rabbit antithymocyte globulin (rATG) are commonly used for induction therapy in renal transplantation. This retrospective, single‐center, cohort study evaluated cumulative incidence of one‐yr biopsy‐proven acute rejection (BPAR) among 200 consecutive primary non‐sensitized kidney transplant recipients who received either alemtuzumab (n = 100) or rATG (n = 100) induction followed by rapid steroid taper, tacrolimus, and mycophenolate mofetil. Protocol biopsies, plasma and urine BK virus PCR, serum creatinine and iothalamate glomerular filtration rate (iGFR), were obtained at 1, 4, and 12 months from transplantation. The one‐yr BPAR rates were similar between the alemtuzumab and rATG groups; however, rejection Banff IA and higher was more common in the alemtuzumab arm (18% vs. 5%, p = 0.047). After adjusting for confounding variables, alemtuzumab was still associated with Banff IA and higher rejection (adjusted OR: 3.7, CI: 1.2–10.5, p = 0.02). Despite similar rates of BK viremia, more patients in the alemtuzumab arm developed BK nephropathy (16% vs. 3%, p = 0.046). One‐year iGFR (53.4 ± 20.2 vs. 71.9 ± 27.2 mL/min/1.73 m², p = 0.002) and three‐yr graft survival (89.5% vs. 95%, p = 0.05) were lower in the alemtuzumab group. In low immunological risk kidney transplant recipients on steroid‐free immunosuppression, alemtuzumab was associated with more severe rejection and BK nephropathy compared to rATG.     

Toll‐Like Receptor 3 and 7/8 Function Is Impaired in Hepatitis C Rapid Fibrosis Progression Post‐Liver Transplantation

Recurrence of hepatitis C (HCV) postliver transplant is universal, with a subgroup developing rapid hepatic fibrosis. Toll‐like receptors (TLRs) are critical to innate antiviral responses and HCV alters TLR function to evade immune clearance. Whether TLRs play a role in rapid HCV recurrence posttransplant is unknown. We stimulated peripheral blood mononuclear cells (PBMCs) from 70 patients with HCV postliver transplant with TLR subclass‐specific ligands and measured cytokine production, TLR expression and NK cell function. Rate of fibrosis progression was calculated using posttransplant liver biopsies graded by Metavir scoring (F0–4; R = fibrosis stage/year posttransplant; rapid fibrosis defined as >0.4 units/year). Thirty of 70 (43%) patients had rapid fibrosis progression. PBMCs from HCV rapid‐fibrosers produced less IFNα with TLR7/8 stimulation (p = 0.039), less IL‐6 at baseline (p = 0.027) and with TLR3 stimulation (p = 0.008) and had lower TLR3‐mediated monocyte IL‐6 production (p = 0.028) compared with HCV slow fibrosers. TLR7/8‐mediated NKCD56 dim cell secretion of IFNγ was impaired in HCV rapid fibrosis (p = 0.006) independently of IFNα secretion and TLR7/8 expression, while cytotoxicity remained preserved. Impaired TLR3 and TLR7/8‐mediated cytokine responses may contribute to aggressive HCV recurrence postliver transplantation through impaired immune control of HCV and subsequent activation of fibrogenesis.     

Outcomes of Steroid‐Avoidance Protocols in Pediatric Kidney Transplant Recipients

Advances in immunosuppression have facilitated increased use of steroid‐avoidance protocols in pediatric kidney transplantation. To evaluate such steroid avoidance, a retrospective cohort analysis of pediatric kidney transplant recipients between 2002 and 2009 in the United Network for Organ Sharing database was performed. Outcomes (acute rejection and graft loss) in steroid‐based and steroid‐avoidance protocols were assessed in 4627 children who received tacrolimus and mycophenolate immunosuppression and did not have multiorgan transplants. Compared to steroid‐based protocols, steroid avoidance was associated with decreased risk of acute rejection at 6 months posttransplant (8.3% vs. 10.9%, p = 0.02) and improved 5‐year graft survival (84% vs. 78%, p < 0.001). However, patients not receiving steroids experienced less delayed graft function (p = 0.01) and pretransplant dialysis, were less likely to be African‐American and more frequently received a first transplant from a living donor (all p < 0.001). In multivariate analysis, steroid avoidance trended toward decreased acute rejection at 6 months, but this no longer reached statistical significance, and there was no association of steroid avoidance with graft loss. We conclude that, in clinical practice, steroid avoidance appears safe with regard to graft rejection and loss in pediatric kidney transplant recipients at lower immunologic risk.     

Living Donor Liver Transplantation for Patients Older Than Age 70 Years: A Single‐Center Experience

Over the past two decades, the age of liver transplantation (LT) recipients has been increasing. We reviewed our experience with LT for patients aged ≥70 years (range: 70–78 years) and investigated the feasibility of performing LT, especially living donor LT (LDLT), for older patients. We retrospectively reviewed the medical records of 25 patients (15 LDLT recipients, 10 deceased donor LT recipients) aged ≥70 years who underwent LT from January 2000 to April 2016. Their perioperative morbidity rate was 28.0%, and the in‐hospital mortality rate was 16.0%; these results were comparable to those of matched patients in their 60s (n = 73; morbidity, p = 0.726; mortality, p = 0.816). For patients in their 70s, the 1‐ and 5‐year patient survival rates were 84.0% and 69.8%, and the 1‐ and 5‐year graft survival rates were 83.5% and 75.1%, respectively. Comparisons of patient and graft survival rates between matched patients in their 60s and 70s showed no statistically significant differences (patient survival, p = 0.372; graft survival, p = 0.183). Our experience suggests that patients aged ≥70 years should not be excluded from LT, or even LDLT, based solely on age and implies that careful selection of recipients and donors as well as meticulous surgical technique are necessary for successful results.     

Negative outcomes after liver transplantation in patients with alcoholic liver disease beyond the fifth post‐transplant year

Although up to 50% of patients with alcoholic liver disease (ALD) resume alcohol consumption after liver transplantation (LT), numerous studies indicate that long‐term results are not compromised. This study focused on evaluating the impact of ALD on outcomes up to and beyond the fifth year after LT. Among the 432 primary LT recipients included in this study, 97 underwent transplantation for ALD. Alcohol relapse rate at 10 yr was 33.5%, with younger recipient age being the only independent predictor (p = 0.019). Survival of patients with ALD (77.0%) was similar to those without (79.0%) up to the fifth post‐transplant year (p = 0.655) but worse during the five subsequent years among the five‐yr survivors (70.6% vs. 92.9%; p = 0.002). ALD was an independent risk factor for poorer survival beyond the fifth post‐transplant year (p = 0.049), but not earlier (p = 0.717). Conversely, alcohol relapse increased the risk of death only during the first five post‐transplant years (p = 0.039). There were no significant differences regarding graft failure incidence between ALD and non‐ALD recipients up to the fifth post‐transplant year (7.3% vs. 11.6%; p = 0.255) and beyond (12.9% vs. 5.0%; p = 0.126). In conclusion, pre‐transplant diagnosis of ALD yields negative effects on post‐transplant outcomes beyond the fifth post‐transplant year, not attributable to recidivism.     

Impact of locoregional therapy and alpha‐fetoprotein on outcomes in transplantation for liver cancer: a UNOS Region 6 pooled analysis

Liver transplantation (LT) provides optimal long‐term disease‐free survival for hepatocellular carcinoma (HCC). High pre‐LT alpha‐fetoprotein (AFP) has been associated with HCC recurrence, but it is unclear whether a drop in AFP or locoregional therapy impacts survival/recurrence after LT. LT‐recipients transplanted for HCC in three centers (UNOS Region 6) were reviewed (2006–2009) for demographics, tumor characteristics, locoregional therapy, AFP, recurrence, and survival. Among 211 LT recipients (mean age 56.4 yr, 83% male, mean MELD 12.2), 94% met Milan criteria and 61% received locoregional therapy. Mean disease‐free survival (DFS) was 1549.7 d, and 84% are currently alive. Factors affecting DFS included recurrence (RR, 0.074; 95% CI, 0.038–0.14), normal peak AFP (29.6, 95% CI, 2.96–296.3), peak AFP >400 (RR, 0.15; 95% CI, 0.03–0.73) and AFP at LT >400 (RR, 15.5; 95% CI, 2.4–100.5). Twenty‐one patients had recurrence and were more likely beyond Milan criteria (5/23(21%) vs. 8/220 (4%), p = 0.0038), with peak AFP >400 and AFP at LT >400 (p = 0.001). Locoregional therapy did not affect mean DFS (1458.0 vs. 1603.8 d, p = 0.05) or recurrence (12.5% vs. 6%). Predictors of recurrence were similar to previous studies, including high AFP and tumor outside Milan criteria. While locoregional therapy itself did not affect DFS/recurrence, a decrease in AFP pre‐transplant appears to positively influence outcomes in those who received locoregional therapy.     

Long‐term results for living donor liver transplant recipients with hepatocellular carcinoma using intraoperative blood salvage with leukocyte depletion filter

Massive intraoperative bleeding during liver transplantation often requires large amounts of blood products. The goal of this study was to investigate long‐term outcomes of living donor liver transplantation (LDLT) recipients with hepatocellular carcinoma (HCC) who underwent intraoperative use of intraoperative blood salvage (IBS) and leukocyte depletion filter (LDF). In this study, we included 230 LDLT recipients with HCC from two transplantation centers, between February 2002 and December 2007. Group 1 patients (n = 121) underwent intraoperative IBS with LDF and group 2 patients (n = 109) did not. The amount of autotransfused, filtered red blood cells (RBCs) in group 1 was 1590.2 ± 1486.8 ml, which corresponded to 5.9 units of allogenic leukocyte‐depleted RBCs saved. The incidences of renal dysfunction, postoperative bleeding, and urinary tract infection in group 2 were higher than in group 1 (P < 0.05). Recurrence‐free survival rates for 1, 3, and 5 years were 91.3%, 83.3%, and 83.3%, respectively, in group 1, and 84.6%, 79.0%, and 77.4%, respectively, in group 2 (P = 0.314). IBS using LDF does not increase the risk of cancer recurrence during LDLT for recipients with HCC. Therefore, the use of IBS with LDF appears to be safe for LDLT recipients with HCC.     

Post‐transplant lymphoproliferative disorder in adult liver transplant recipients: a South American multicenter experience

Post‐transplant lymphoproliferative disorder (PTLD) is a major and potentially life‐threatening complication after solid‐organ transplantation. The aim of this study was to describe the disease characteristics, clinical practices, and survival related to PTLD in adult orthotopic liver transplant (OLT) recipients in South America. We conducted a survey at four different transplant groups from Argentina, Brazil, and Chile. Among 1621 OLT recipients, 27 developed PTLD (1.7%); the mean age at diagnosis was 53.7 (±14) yr with a mean time of 39.7 (±35.2) months from OLT to PTLD diagnosis. Initial therapy included reduction in immunosuppression alone in 23.1% of the patients. Either rituximab or chemotherapy was employed as initial or second‐line therapy in 76.9% of the patients. PTLD location was frequently extranodal (80.7%) and mostly involving the transplanted liver (59.3%). The overall survival at one and five yr post‐PTLD diagnosis was 53.8% and 46.2%, respectively. Significant univariate risk factors for post‐PTLD mortality included lactate dehydrogenase ≥250 U/L (HR 9.66, p = 0.02), stage III/IV PTLD (HR 5.34, p = 0.004), and HCV infection (HR 7.68, p = 0.01). In conclusion, PTLD in OLT adult recipients is predominantly extranodal, and although mortality is high, long‐term survival is possible.     

Early emergence of anti‐HCV antibody implicates donor origin in recipients of an HCV‐infected organ

Hepatitis C virus (HCV) seroconversion among HCV‐uninfected transplant recipients from HCV‐infected (NAT+/Antibody+) or HCV‐exposed (NAT?/Antibody+) donors has been reported. However, the origin of anti‐HCV antibody and the implications of seroconversion remain unknown. We longitudinally tested plasma from HCV‐uninfected kidney (n = 31) or heart transplant recipients (n = 9) of an HCV NAT+ organ for anti‐HCV antibody (both IgG and IgM isotypes). Almost half of all participants had detectable anti‐HCV antibody at any point during follow‐up. The majority of antibody‐positive individuals became positive within 1‐3 days of transplantation, and 6 recipients had detectable antibody on the first day posttransplant. Notably, all anti‐HCV antibody was IgG, even in samples collected posttransplant day 1. Late seroconversion was uncommon (≈20%‐25% of antibody+ recipients). Early antibody persisted over 30 days in kidney recipients, whereas early antibody dropped below detection in 50% of heart recipients within 2 weeks after transplant. Anti‐HCV antibody is common in HCV‐uninfected recipients of an HCV NAT+ organ. The IgG isotype of this antibody and the kinetics of its appearance and durability suggest that anti‐HCV antibody is donor derived and is likely produced by a cellular source. Our data suggest that transfer of donor humoral immunity to a recipient may be much more common than previously appreciated.     

Renal outcomes of simultaneous liver–kidney transplantation compared to liver transplant alone for candidates with renal dysfunction

It is unclear whether a concomitant kidney transplant grants survival benefit to liver transplant (LT) candidates with renal dysfunction (RD). We retrospectively studied LT candidates without RD (n = 714) and LT candidates with RD who underwent either liver transplant alone (RD‐LTA; n = 103) or simultaneous liver–kidney transplant (RD‐SLKT; n = 68). RD was defined as renal replacement therapy (RRT) requirement or modification of diet in renal disease (MDRD)–glomerular filtration rate (GFR) <25 mL/min/1.73 m². RD‐LTAs had worse one‐yr post‐transplant survival compared to RD‐SLKTs (79.6% vs. 91.2%, p = 0.05). However, RD‐LTA recipients more often had hepatitis C (60.2% vs. 41.2%, p = 0.004) and more severe liver disease (MELD 37.9 ± 8.1 vs. 32.7 ± 9.1, p = 0.0001). Twenty RD‐LTA recipients died in the first post‐transplant year. Evaluation of the cause and timing of death relative to native renal recovery revealed that only four RD‐LTA recipients might have derived survival benefit from RD‐SLKT. Overall, 87% of RD‐LTA patients recovered renal function within one month of transplant. One yr after RD‐LTA or RD‐SLKT, serum creatinine (1.5 ± 1.2 mg/dL vs. 1.4 ± 0.5 mg/dL, p = 0.63) and prevalence of stage 4 or 5 chronic kidney disease (CKD; 5.9% vs. 6.8%, p = 0.11) were comparable. Our series provides little evidence that RD‐SLKT would have yielded substantial short‐term survival benefit to RD‐LTA recipients.