Christine A. O’Mahony

Liver transplantation in autoimmune liver diseases

Liver transplantation is indicated for terminal phases of autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. Indications for transplantation in autoimmune liver diseases are similar to those used in other acute or chronic liver diseases. Therapeutic advances have reduced the need for transplantation for autoimmune hepatitis and primary biliary cirrhosis but not for primary sclerosing cholangitis. Overall, outcomes of transplantation for autoimmune liver diseases are excellent. However, recurrence of autoimmune liver diseases in the allograft has variable impacts on graft and patient survivals. Treatment of recurrent diseases requires changes in immunosuppression or addition of ursodeoxycholic acid. Among autoimmune liver diseases, only autoimmune hepatitis occurs de novo in recipients transplanted for other diseases. Patients transplanted for autoimmune hepatitis or primary sclerosing cholangitis are at risk for reactivation or de novo onset of ulcerative colitis. Better understanding of the pathogenesis of recurrent autoimmune liver diseases is needed to devise effective means of prevention and treatment.

Liver transplantation with donation after cardiac death donors: A comprehensive update

BACKGROUND Use of donation after cardiac death (DCD) donors has been proposed as an effective way to expand the availability of hepatic allografts used in orthotopic liver transplantation (OLT); yet, there remains no consensus in the medical literature as to how to choose optimal recipients and donors based on available information. METHODS We queried the United Network of Organ Sharing/Organ Procurement and Transplantation Network database for hepatic DCD allografts used in OLT. As of March 31, 2011, 85,148 patients received hepatic allografts from donation-after-brain-death (DBD) donors, and 2351 patients received hepatic allografts from DCD donors. We performed survival analysis using log-rank and Kaplan-Meier tests. We performed univariate and multivariate analyses using the Cox proportional hazards model. All statistics were performed with SPSS 15.0. RESULTS Patients receiving hepatic DCD allografts had significantly worse survival compared with patients receiving hepatic DBD allografts. Pediatric patients who received a hepatic DCD allograft had similar survival to those who received a hepatic DBD allograft. The optimal recipient-related characteristics were age <50 y, International Normalized Ratio <2.0, albumin >3.5 gm/dL, and cold ischemia time <8 h; optimal donor-related characteristics included age <50 y and donor warm ischemia time <20 min. CONCLUSIONS By identifying certain characteristics, the transplant clinicians decision-making process can be assisted so that similar survival outcomes after OLT can be achieved with the use of hepatic DCD allografts.

Extended Donors in Liver Transplantation

Several criteria are used to differentiate between standard and extended allograft donors. These criteria include deceased after cardiac death, advanced donor age, steatosis, previous malignancy in the donor, hepatitis C virus-positive allografts, human T-cell lymphotropic virus-positive allografts, active infections in the donor, high-risk donors, split liver transplantations, and living donor liver transplantations. Review of the literature can lead each practitioner to incorporate extended criteria donors into their transplant program, thereby individualizing the use of these allografts, increasing the donor pool, and decreasing overall waitlist mortality.

Pediatric liver transplantation for primary malignant liver tumors with a focus on hepatic epithelioid hemangioendothelioma: The UNOS experience

Guiteau JJ, Cotton RT, Karpen SJ, O’Mahony CA, Goss JA. Pediatric liver transplantation for primary malignant liver tumors with a focus on hepatic epithelioid hemangioendothelioma: The UNOS experience.
Pediatr Transplantation 2010: 14: 326–331.

Building a Comprehensive Genomic Program for Hepatocellular Carcinoma

BackgroundHepatocellular carcinoma (HCC) is the most common primary liver cancer, causing approximately 660,000 deaths worldwide annually. The preferred treatment of HCC is surgical resection or orthotopic liver transplantation (OLT) for patients meeting specific criteria. For patients outside these criteria, options are limited and include medical therapy, radiofrequency ablation, chemoembolization, or palliative measures, and these result in poor outcomes. Various centers at Baylor are elucidating the genomics of HCC to improve treatment options, with a focus on three etiologies: hepatitis C virus, hepatitis B virus, and non-viral.MethodsThrough collaborative efforts, we have established an effective specimen biobanking protocol, and we are using several techniques to analyze HCC, including whole genome sequencing, whole exome sequencing, gene-specific analysis, gene expression, and epigenetic analysis.ResultsWe have completed whole genome sequencing on two patient samples, whole exome sequencing on 47 patient samples, gene-specific analysis on 94 patient samples, gene expression on 4 patient samples, and epigenetic analysis on 1 patient sample.ConclusionsWe hope to use these results to define novel genetic therapeutic strategies that may work in conjunction with surgical approaches to improve long-term patient and graft survival rates in patients with HCC. We also aim to provide a functional framework of a comprehensive program for genomic analysis that may be imitated by other institutions and for other tumors in the global quest toward personalized genomic medicine.

Comparing Outcomes for Rare Primary Hepatic Tumors after Liver Transplantation

Aim: Liver transplantations (LT) have proven to be a successful treatment for many tumors of the liver. The goal of this study was to evaluate the outcomes of liver transplantations in patients with primary liver tumors with a focus on rarer malignancies. Methods: The UNOS database catalogues all adult patients who underwent LT for a primary liver tumor from 1992-2008. Of the 73,231 liver transplantations, 5,682 patients with liver tumors were identified and categorized by indication for LT: hepatocellular carcinoma (HCC, n=5272), hepatic epithelioid hemangioendothelioma (HEH, n=85), cholangiocarcinoma (n=249), sarcomas (n= 11) and combined HCC-Cholangiocarcinomas (HCC-CC, n=12). Survivals were calculated using Kaplan-Meier and log rank tests. Results: 5,629 patients received LT for solid liver tumors. HCC patients and their allografts survived longer than those transplanted for cholangiocarcinomas (p=0.001, 0.002) or for HCC-CC (p=0.025, 0.004). Overall survival rates of HCC patients were 86.4%, 71.3%, and 61.2% at 1, 3 and 5 years, respectively. Cholangiocarcinoma patients had survival rates of 79.7%, 60.3% and 45.5% at 1-, 3- and 5-years from transplant. HCC-CC patients had the worst overall survival of 72.9%, 39.1% and 39.1% at 1, 3 and 5 years. Allograft survival in HCC-CC patients was comparatively low, averaging 65.6%, 35.2% and 0% at 1-, 3- and 5-years. HEH patients and their allografts survived the longest with overall survival of 83.9%, 77.8% and 73.5% at 1, 3 and 5 years, respectively, and allograft survival at 76.8%, 69.8% and 64.3%. Conclusion: Our data reveals overall survival was significantly better in HEH patients when compared to HCC, cholangiocarcinoma and HCC-CC patients after LT. In fact, HCC-CC patients fared the worst, both in patient and allograft survival, as compared to HCC and HEH. Results of cholangiocarcinoma patients show worse survival after LT compared to HCC and HEH, though recent evidence suggests adjuvant therapy will change outcomes for the future. Our findings suggest transplantation for HCC-CC may not be sufficient treatment. Other forms of adjuvant and neoadjuvant therapy may be indicated, warranting further research.

Biliary Reconstruction in Pediatric Liver Transplantation: A Case Report of Biliary Complications and Review of the Literature

With the advent of segmental liver allografts from liver donors, reduced-size cadaveric allografts, and split cadaveric allografts, pediatric pre-transplantation patient mortality has reduced. However, this expansion of the donor pool for size-appropriate allografts for patients with end-stage liver disease has led to an increased incidence of biliary complications. We performed a retrospective review of our series of 242 pediatric patients who received a liver transplantation. Biliary complications at our institution are presented, with a review of the current literature identifying risk factors that predispose pediatric liver transplant patients to biliary complications. We present the protocol used at our institution to minimize risk of biliary complications in our pediatric post-operative patient population.

Liver transplantation as definitive treatment of an unresectable mesenchymal hamartoma in a child with Beckwith–Wiedemann Syndrome

Abstract Mesenchymal liver hamartomas are benign tumors that can cause life-threatening abdominal distension and carry a risk for malignant transformation. In this case report, we describe a 13-month-old male with Beckwith–Wiedemann Syndrome (BWS) who presented with multiple mesenchymal liver hamartomas causing severe intra-abdominal mass effect. Imaging revealed six large multi-locular cystic lesions, ranging from 3.8 to 8.9 cm in diameter. The large size and spread of the tumors necessitated liver transplantation for complete removal. The patient successfully underwent cadaveric piggyback liver transplantation at 25 months of age. He was alive at 16-month follow-up without evidence of tumor recurrence or graft rejection. Histological examination of the hepatic masses revealed mucinous epithelial lining and abundant hepatocytes in varying stages of differentiation, supporting the diagnosis of mesenchymal hamartoma. To the best of our knowledge, this is the first reported case of liver transplantation in a patient with BWS as definitive treatment for unresectable mesenchymal liver hamartoma.

A Primer on a Hepatocellular Carcinoma Bioresource Bank Using the Cancer Genome Atlas Guidelines: Practical Issues and Pitfalls

BackgroundSince the advent of the human genome, the era of personalized genomic medicine is indisputably in progress.MethodsIn an effort to contribute to the evolving knowledge of genomic medicine, we have aimed directly at building a bioresource bank for hepatocellular carcinoma. This tumor bank is based on the rigorous guidelines set forth by the National Cancer Institute, and it offers analytes to help elucidate the mechanisms of progression from cirrhosis to malignancy, risk factors for recurrence, and applicability of current treatment options to a diverse group of people.ConclusionsSurgeons have a privileged position between patients (and their cancer) and the benches of basic science. Thus, we offer a primer based on our own experiences, from which surgeons may take elements to build their own bioresource bank for use in collaboration with others. We highlight some practicalities and pitfalls that could be overlooked, as well as a discussion of possible solutions.

Biliary epithelial metastasis of squamous carcinoma of the anus

IntroductionThe liver and biliary tree are common sites of initial metastasis for many primary tumors. However, we recently encountered a patient who presented with biliary-tree tumor encasement as a first metastasis from squamous carcinoma of the anus.MethodsTo our knowledge, this has not been previously described in the literature.ConclusionsAs obstructive jaundice is a relatively common presenting sign in the emergency room and in general surgical clinics, we thus recommend early consideration of metastatic disease as a differential diagnosis in patients post-chemoradiotherapy for anal carcinoma who present with obstructive jaundice.