Hepatocellular carcinoma (HCC) remains a common cause of mortality worldwide. Liver transplantation has emerged as the optimal treatment for cirrhotic patients with HCC; however, the shortage of donor organs leaves waitlisted patients at risk for disease progression beyond transplant criteria. Prevention of waitlist dropout has fueled investigation into a wide array of locoregional therapies for the management of HCC in candidates awaiting liver transplantation. We present a patient with HCC who underwent treatment with sorafenib, which resulted in a remarkable reduction in tumor burden to allow for liver transplant listing.

Background

Graft-vs-host disease (GVHD) is a rare and often fatal complication of orthotopic liver transplantation (OLT). The skin is frequently involved early in disease progression, but clinical and histopathological features may be nonspecific, presenting a diagnostic challenge. While the detection of peripheral blood chimerism has been proposed as a diagnostic criterion for post-OLT GVHD, it is not known whether peripheral blood chimerism is an absolute requirement for the diagnosis.

Materials and methods

We report a case of a 57-year-old man who developed post-OLT GVHD with cutaneous, enteric, and bone marrow involvement. We also review the epidemiology, pathogenesis, clinical presentation, histopathology, molecular diagnostic techniques, and treatment of GVHD following liver transplantation.

Results

In our patient, analysis of the peripheral blood by short-tandem repeat polymerase chain reaction did not detect circulating donor lymphocytes. Donor lymphocytes were detected in the buccal mucosa, however, confirming the diagnosis. A review of chimerism patterns in 63 previously published cases of post-OLT GVHD reveals that this is the first reported case in which chimerism was absent in the peripheral blood but present in another site.

Conclusions

Peripheral blood chimerism may be absent in cases of post-OLT GVHD. A combination of clinical, histopathological, and molecular features is therefore required to make this challenging diagnosis.

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 m(2) . 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.

A subset of liver transplantation (LT) recipients who undergo transplantation for hepatocellular carcinoma (HCC) will develop postoperative recurrence. There has yet to be a thorough investigation of donor factors influencing recurrence. Data regarding adult, primary LT recipients with HCC (n = 5002) who underwent transplantation between January 1, 2006 and September 30, 2010 were extracted from the United Network for Organ Sharing database, and the cumulative incidence of post-LT recurrence by donor factors was subsequently estimated. Among the HCC LT recipients, 324 (6.5%) developed recurrence. An analysis of donor characteristics demonstrated a higher cumulative incidence of recurrence within 4 years of transplantation among recipients with donors ≥ 60 years old (11.8% versus 7.3% with donors < 60 years old, P < 0.001) and with donors from a nonlocal share distribution (10.6% versus 7.4% with donors with a local share distribution, P = 0.004). The latter 2 findings held true in a multivariate analysis: the risk of HCC recurrence increased by 70% for recipients of livers from donors ≥ 60 years old [subhazard ratio (SHR) = 1.70, 95% confidence interval (CI) = 1.31-2.20, P < 0.001] and by 42% for recipients of nonlocal share distribution livers (SHR = 1.42, 95% CI = 1.09-1.84, P = 0.009) after adjustments for clinical characteristics. In conclusion, the consideration of certain donor factors may reduce the cumulative incidence of posttransplant HCC recurrence and thus improve long-term survival after LT.

Background

Successful left lateral segment (sectionectomy) and right trisegmentectomy (trisectionectomy) split-liver transplantation (SLT) have been achieved. However, there are few reports of the use of true right/left splitting in SLT.

Methods

A single-centre retrospective review of true right/left ex vivo split-liver transplants performed during the period 1993-2010 was conducted. Nine cadaveric liver grafts underwent splitting and the resultant 18 allografts were used in transplants performed at the study centre.

Results

In the nine right lobe recipients, 10-year patient and graft survival rates were both 74%. There were no vascular complications, one biliary complication and one re-exploration. In the nine left lobe recipients, 10-year patient and graft survival rates were 78% and 66%, respectively. Postoperative complications included six biliary complications, four of which required surgical revision and all of which occurred within 5 months of transplantation, and two vascular complications, including one early hepatic artery thrombosis (HAT) and one late HAT, one of which required retransplantation. Five left lobe recipients required re-exploration, and one patient developed small-for-size syndrome following SLT, which resolved with conservative measures.

Conclusions

True right/left ex vivo SLT remains a viable option for facilitating the expansion of the adult cadaver donor pool and allows for excellent patient and graft survival. Postoperative morbidity remains high, especially in recipients of the left lobe graft, and must be balanced with the benefits to be derived from transplant.

Older donor age is associated with lower graft and patient survival among all recipients of liver transplantation (LT). Among patients with hepatitis C virus (HCV), donor age is one of the strongest predictors of fibrosis severity and graft loss. We evaluated the implementation of a donor age restriction policy for LT patients with HCV at a single center and the effects that this policy had on wait-list (WL) and post-LT outcomes for HCV and non-HCV patients. This was a cohort study of 2388 WL patients and 1015 LT recipients between March 2002 and January 2013 and reflected 3 different eras of donor age policies. With the donor age restriction, the median donor age was reduced in LT recipients with HCV versus LT recipients without HCV (30 versus 48 years, P < 0.001) without differences in the WL time (10.6 versus 8.0 months, P = 0.23). According to a competing risks regression, those with HCV and those without HCV had lower subhazard ratios (SHRs) of dropout or death on the WL during the donor age restriction era versus the era without donor age restriction [SHR = 0.68 (P < 0.01) and SHR = 0.64 (P = 0.01), respectively]. No differences were seen in early post-LT survival for patients with or without HCV between eras (P = 0.7 and P = 0.88, respectively). In conclusion, we show that donor age restriction for HCV results in a lower donor age for HCV recipients without obvious adverse WL consequences. Although additional studies are needed, our results demonstrate the feasibility of donor age restriction for LT recipients with HCV, and such information may be relevant to programs with limited access to new antiviral therapies for which modifying the risk of severe disease remains of paramount importance.

Background

Geographic disparity in access to liver transplantation (LT) exists. This study sought to examine Model for End-Stage Liver Disease-era multiply listed (ML) LT candidate (ie, candidates who list at 2 or more LT centers to receive a liver transplant).

Study design

Data on adult, primary, non-status 1 LT candidates (n = 59,557) listed from January 1, 2005 to December 31, 2011 were extracted from the United Network for Organ Sharing's Standard Transplant Analysis and Research files. Comparisons of ML vs singly listed LT candidates were performed, with additional analysis performed at the donor service area (DSA) and regional level, as well as assessment of the donor population used.

Results

There were 1,358 (2.3%) ML candidates during the 7-year study period. Multiply listed candidates compared with singly listed candidates were more often male, white, blood type O, nondiabetic, college educated, and privately insured. The odds of pursuing ML increased considerably as time on the waitlist increased. Of the ML candidates, 918 (67.6%) went on to receive a liver transplant (ML-LT), 767 (83.6%) at the secondary listing DSA, which was a median of 588 miles (range 229 to 1095 miles) from the primary listing DSA. When compared with the primary listing DSA, the secondary listing DSA had significantly lower match Model for End-Stage Liver Disease scores, as well as shorter wait times. Regional analysis demonstrated significantly higher odds for pursuing ML from LT candidates located within regions 1, 5, and 9.

Conclusions

A small and distinctive cohort of LT candidates pursue ML, indicating willingness and means to travel to receive a liver transplant. Efforts toward equalizing LT access across regional disparities are warranted, and can help obviate the need for ML.

Introduction

Cavernous hemangiomas represent the most common benign primary hepatic neoplasm, often being incidentally detected. Although the majority of hepatic hemangiomas remain asymptomatic, symptomatic hepatic hemangiomas can present with abdominal pain, hemorrhage, biliary compression, or a consumptive coagulopathy. The optimal surgical management of symptomatic hepatic hemangiomas remains controversial, with resection, enucleation, and both deceased donor and living donor liver transplantation having been reported.

Case report

We report the case of a patient found to have a unique syndrome of multiorgan cavernous hemangiomatosis involving the liver, lung, omentum, and spleen without cutaneous involvement. Sixteen years following her initial diagnosis, the patient suffered from intra-abdominal hemorrhage due to her giant cavernous hepatic hemangioma. Evidence of continued bleeding, in the setting of Kasabach-Merritt Syndrome and worsening abdominal compartment syndrome, prompted MELD exemption listing. The patient subsequently underwent emergent liver transplantation without complication.

Conclusion

Although cavernous hemangiomas represent the most common benign primary hepatic neoplasm, hepatic hemangioma rupture remains a rare presentation in these patients. Management at a center with expertise in liver transplantation is warranted for those patients presenting with worsening DIC or hemorrhage, given the potential for rapid clinical decompensation.

Background and aims

The beneficial effect of one graft on another has been reported in combined transplantation but the associated mechanisms and biological influence of each graft have not yet been established.

Methods

In multiple analyses, we explored the PBMC phenotype and signature of 45 immune-related messenger RNAs and 754 microRNAs from a total of 235 patients, including combined liver-kidney transplant recipients (CLK), patients with a liver (L-STA) or kidney (K-STA) graft only under classical immunosuppression and patients with tolerated liver (L-TOL) or kidney grafts (K-TOL).

Results

CLK show an intermediary phenotype with a higher percentage of peripheral CD19(+) CD24(+) CD38(Low) memory B cells and Helios(+) Treg cells, two features associated with tolerance profiles, compared to L-STA and K-STA (P < 0.05, P < 0.01). Very few miRNA were significantly differentially expressed in CLK vs. K-STA and even fewer when compared to L-STA (35 and 8, P < 0.05). Finally, CLK are predicted to share common miRNA targets with K-TOL and even more with L-TOL (344 and 411, P = 0.005). Altogether CLK display an intermediary phenotype and gene profile, which is closer to that of liver transplant patients, with possible similarities with the profiles of tolerant patients.

Conclusion

These data suggest that CLK patients show the immunological influence of both allografts with liver having a greater influence.