Search

Source and cell culture information for cell lines.

Supplementary Figure S1. IDHm ICC are insensitive to IDH inhibition. Supplementary Figure S2. Similarity matrix for drug response of BTC cell lines. Supplementary Figure S3. Hypersensitivity of ICC cells harboring endogenous IDH mutations to dasatinib. Supplementary Figure S4. Torin 1 inhibits growth of ICC cell lines. Supplementary Figure S5. Critical role for SRC in IDHm ICC cells. Supplementary Figure S6. Ectopic expression of mutant IDH has only a modest effect on dasatinib sensitivity.

Background During cancer operations, the cancer itself is often hard to delineate—buried beneath healthy tissue and lacking discernable differences from the surrounding healthy organ. Long-wave infrared, or thermal, imaging poses a unique solution to this problem, allowing for the real-time label-free visualization of temperature deviations within the depth of tissues. The current study evaluated this technology for intraoperative cancer detection. Methods In this diagnostic study, patients with gastrointestinal, hepatobiliary, and renal cancers underwent long-wave infrared imaging of the malignancy during routine operations. Results It was found that 74% were clearly identifiable as hypothermic anomalies. The average temperature difference was 2.4°C (range 0.7 to 5.0) relative to the surrounding tissue. Cancers as deep as 3.3 cm from the surgical surface were visualized. Yet, 79% of the images had clinically relevant false positive signals [median 3 per image (range 0 to 10)] establishing an accuracy of 47%. Analysis suggests that the degree of temperature difference was primarily determined by features within the cancer and not peritumoral changes in the surrounding tissue. Conclusion These findings provide important information on the unexpected hypothermal properties of intra-abdominal cancers, directions for future use of intraoperative long-wave infrared imaging, and new knowledge about the in vivo thermal energy expenditure of cancers and peritumoral tissue.

Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver bile duct malignancy exhibiting frequent isocitrate dehydrogenase (IDH1/IDH2) mutations. Through a high-throughput drug screen of a large panel of cancer cell lines, including 17 biliary tract cancers, we found that IDH mutant (IDHm) ICC cells demonstrate a striking response to the multikinase inhibitor dasatinib, with the highest sensitivity among 682 solid tumor cell lines. Using unbiased proteomics to capture the activated kinome and CRISPR/Cas9-based genome editing to introduce dasatinib-resistant “gatekeeper” mutant kinases, we identified SRC as a critical dasatinib target in IDHm ICC. Importantly, dasatinib-treated IDHm xenografts exhibited pronounced apoptosis and tumor regression. Our results show that IDHm ICC cells have a unique dependency on SRC and suggest that dasatinib may have therapeutic benefit against IDHm ICC. Moreover, these proteomic and genome-editing strategies provide a systematic and broadly applicable approach to define targets of kinase inhibitors underlying drug responsiveness.Significance: IDH mutations define a distinct subtype of ICC, a malignancy that is largely refractory to current therapies. Our work demonstrates that IDHm ICC cells are hypersensitive to dasatinib and critically dependent on SRC activity for survival and proliferation, pointing to new therapeutic strategies against these cancers. Cancer Discov; 6(7); 727–39. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 681

Background The role of staging laparoscopy in pancreatic cancer in the age of high-resolution CT scans is under debate. This study's aim is to evaluate the efficacy of staging laparoscopy in this disease. Study Design A retrospective cohort study was conducted evaluating patients who underwent operative treatment for radiographic stage I to III pancreatic cancer between July 2003 and October 2012. Radiographic follow-up was 94% at 6 months. Results Of 274 patients who met inclusion criteria, 136 underwent staging laparoscopy, which identified radiographic occult distant metastases in 2% (3 of 136). However, subsequent laparotomy identified an additional 9% (12 of 136) harboring distant metastases in regions not visualized on standard staging laparoscopy; specifically, the posterior liver surface, paraduodenal retroperitoneum, proximal jejunal mesentery, and lesser sac. The remaining 138 patients underwent initial staging laparotomy, which showed similar results identifying radiographic occult distant disease in 11% (15 of 138). Within 6 months after the operation, peritoneal or subcapsular liver metastases developed in an additional 6% (15 of 257)—disease that potentially could have been diagnosed at the time of operation—providing a false-negative rate of 88% for staging laparoscopy compared with 36% for staging laparotomy. Conclusions Despite the availability of high-resolution CT scans, occult distant metastases can still be found in 11% of patients during the operation. In the absence of reliable risk factors to predict distant metastases, staging laparoscopy should be offered to all patients with radiographic localized disease. However, the results favor extended laparoscopic staging with evaluation of the posterior liver surface, mobilization of the duodenum, evaluation of the proximal jejunal mesentery, and visualization of the lesser sac.

Background. Correct recognition of the extrahepatic bile ducts is thought to be crucial to reduce the risk of bile duct injuries during various laparoscopic procedures. Image-enhanced laparoscopy techniques, utilizing various optical modalities other than white light, may help in detecting structures “hidden” underneath connective tissue. Methods. A systematic literature search was conducted of studies describing image-enhanced laparoscopy techniques for visualization of the extrahepatic bile ducts. Results. In all, 29 articles met inclusion criteria. They describe various techniques in the animal or human setting, including autofluorescence imaging, drug-enhanced fluorescence imaging, infrared thermography, and spectral imaging. This review describes these various techniques and their results. Conclusion. Image-enhanced laparoscopy techniques for real-time visualization of extrahepatic bile ducts are still in its infancy. Out of the techniques currently described, indocyanine green–enhanced near-infrared fluorescence laparoscopy has the most mature results, but other techniques also appear promising. It can be expected that in the future, image-enhanced laparoscopy might become a routine adjunct to any white-light laparoscopic operation near the hepatic hilum.

Understanding the environment of industrial marketing and how decisions are made in regard to suppliers and products involves a basic knowledge of what the industrial marketplace is, how it differs from consumer markets and behavior, and how factors unique to the industrial buying environment interact to influence ultimate buying decisions. Three models of organizational buying behavior are used to illustrate the development of effective industrial marketing strategy.

The writer offers a new approach for case method teaching which incorporates the more direct application of marketing theories to actual problem-solving scenarios. A matrix model for analyzing cases distinguishes between the form of analysis and the substance of a problem and concomitant alternative approaches to solution.

Prematurity and very low birthweight have often been considered relative contraindications to neonatal organ donation. Organ procurement from neonatal donors is further complicated by unclear guidelines regarding neonatal brain death. We report a successful case of multivisceral transplantation using a graft from a 10-day-old, 2.9 kg, neonatal donor born at 36 6/7 wk in a 3.2 kg, three month old with intestinal and liver failure secondary to midgut volvulus. There was immediate liver graft function with correction of recipient coagulopathy, but delayed normalization of laboratory values and delayed return of bowel function. At six-yr post-transplant follow-up, the patient has normal intestine and liver function. Her last histologically confirmed rejection episode was 30 months prior to last follow-up. This case suggests that multivisceral grafts from very young or small neonatal donors may be transplanted successfully in selected cases. We propose a re-examination of the brain death guidelines for premature and young infants to potentially increase the availability of organs for infant recipients.

Pomposelli JJ, Akoad M, Khwaja K, Lewis WD, Cheah YL, Verbesey J, Jenkins RL, Pomfret EA. Evolution of anterior segment reconstruction after live donor adult liver transplantation: a single-center experience. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01529.x. © 2011 John Wiley & Sons A/S. Abstract: Controversy exists regarding the best method for venous outflow reconstruction after live donor liver transplantation using right lobe grafts. Some authors advocate routine inclusion of the middle hepatic vein with the graft, whereas others favor a more selective approach. In this report, we examine the evolution of our decision making and technique of selective anterior venous segment reconstruction during live donor adult liver transplantation performed in 226 recipients. We have developed a simplified back-bench procedure using sequential-composite anastomosis using various vascular conduits with syndactylization to the right hepatic vein creating a single large-outflow anastomosis in the recipient. Conduits used include iliac artery or vein allograft, recanalized umbilical vein, cryopreserved iliac artery allograft, and 6-mm synthetic expanded polytetrafluoroethylene vascular graft. This technique can be performed quickly, safely, and under cold storage conditions and results in excellent outcome while minimizing donor risk.

In regions with a limited deceased donor pool, living donor adult liver transplantation (LDALT) has become an important treatment modality for patients with hepatocellular carcinoma (HCC) and cirrhosis. Studies have shown higher recurrence rates of HCC after LDALT in comparison with deceased donor liver transplantation (DDLT). The aim of our study was to examine the outcome results and recurrence rates for patients with HCC who underwent LDALT at our center. During an 8-year period, 139 patients underwent LDALT, of whom 28 (20.1%) had HCC in their explanted livers. The median follow-up was 40.8 months. The mean explant tumor size was 3.3 ± 1.2, and the mean number of tumors was 1.5 ± 0.8. Twenty-one patients (75%) had tumors within the Milan criteria, 5 patients had tumors outside the Milan criteria but within the University of California San Francisco (UCSF) criteria, and 2 patients were beyond the UCSF criteria. The overall 1- and 5-year patient and graft survival rates were 96% and 81%, respectively. Survival following LDALT was significantly better than survival following DDLT for HCC during the same time period (P = 0.02). Eight patients (28.6%) developed tumor recurrence. Poor differentiation of tumor cells was the most significant determinant of recurrence. Despite high recurrence rates of HCC following LDALT, overall 5-year survival appears to be excellent. Liver Transpl 15:1861–1866, 2009. © 2009 AASLD.

Cholestatic allograft dysfunction following liver transplantation (LT) can result from many different underlying pathogenetic mechanisms and is a major cause of morbidity and graft loss. Although recurrence of primary sclerosing cholangitis (PSC) is a described entity following LT, the diagnosis is difficult and requires exclusion of common risk factors for stricture formation. There are no reports in the literature of de novo PSC arising in a patient who did not have that disease prior to transplantation. Reported herein is the case of a patient who underwent transplantation for end-stage cryptogenic cirrhosis and who had no underlying risk factors, but who developed late post-LT cholestatic disorder with non-anastomotic biliary strictures. The combined clinical, radiological, and pathological findings resembled those of PSC. Admittedly, it is a challenging proposition but the possibility of a de novo PSC-like syndrome in this patient is raised. A recurrence in a patient who may have had a burnt-out, PSC-like syndrome presenting as cryptogenic cirrhosis, however, cannot be entirely excluded.

Hilar cholangiocarcinoma is a rare malignancy that occurs at the bifurcation of the bile ducts. Complete surgical excision with negative histologic margins remains the only hope for cure or long-term survival. Because of its location and proximity to the vascular inflow of the liver, surgical resection is technically difficult and may require advanced vascular reconstructions to achieve complete excision. Patients who are not candidates for resection should undergo palliative biliary drainage. The role of neoadjuvant therapy and liver transplantation in the management of hilar cholangiocarcinoma remains to be defined in light of the recent promising results.

Summary Clinicopathologic trends of recurrent hepatitis C after liver transplantation (LT) in hepatitis C (HCV) patients seem to have changed in recent years. Our aims were to define the current post-LT patterns of HCV recurrence and identify features of diagnostic and/or prognostic significance. Detailed analysis was performed on 92 HCV patients who underwent LT from June 1999 to December 2003 and survived early post-LT period. The study patients were grouped, as follows: no histologic recurrence (n = 31), “typical” recurrent HCV (n = 52), and post-LT autoimmune-like hepatitis (“AIH-like”) (n = 9). The typical and AIH-like groups had mostly common features with post-LT progressive fibrosis (stage ≥2) more frequent in the latter. Based on post-LT progressive fibrosis (stage ≥2), the 2 post-LT hepatitis categories were regrouped as progressive (n = 24) and nonprogressive (n = 37). High viral counts, HCV genotype 1, and native liver inflammation grade 2 or higher with plasmacytic periseptitis were more frequent in progressive cases than nonprogressive or nonrecurrent cases. Sex mismatch of male recipient and female donor was more common in nonrecurrent group. Overall, death rate was comparable in all groups; however, post-LT HCV-related deaths were more common in progressive cases. In conclusion (1) two thirds (66.2%) of HCV patients developed histologic hepatitis after LT with either typical or AIH-like features; (2) progressive fibrosis was seen in 39.3% of patients with post-LT hepatitis and 26% of the entire study group and was more frequent in AIH-like cases; (3) inflammation grade 2 or higher with plasmacytic periseptitis in native livers may be a predictor of post-LT progressive fibrosis; and (4) male recipient/female donor combination was more common in nonrecurrent cases.

BACKGROUND: Selection of cancer treatment fundamentally relies on staging of the underlying malignancy. The aim of this study was to evaluate the feasibility and effectiveness of laparoscopic narrow band imaging (NBI) for operative staging and detection of occult peritoneal cancer metastases. METHODS: A randomized, controlled feasibility trial with crossover design evaluating adult patients with gastrointestinal or gynecologic malignancies who have a clinical indication for diagnostic laparoscopy was conducted. Twenty-three patients were randomized to white-light followed by NBI laparoscopy (n = 11) or NBI followed by white-light laparoscopy (n = 12) using the Olympus Evis Exera II system. Three patients were excluded from analysis. RESULTS: In all 20 study patients, the abdominal cavity was sufficiently illuminated. An enhanced contrast of microvasculature and organ surface pattern was appreciated. Eight of the 20 patients (40 %) were found to have metastases of the peritoneal surface. While NBI did not show any additional peritoneal lesions, 2 of the 63 suspicious-appearing nodules seen on white-light imaging were not visible on NBI (p = 0.50). The median diameter of all the nodules identified was 2 mm (range 1–50 mm) and was identical with each method. CONCLUSIONS: The information from this feasibility study demonstrated that NBI provides adequate illumination of the abdominal cavity and a unique contrast that enhances microvasculature and architectural surface pattern. The results suggest that NBI laparoscopy is not superior in detecting peritoneal metastases compared to standard white-light laparoscopy, but might provide a technology that could be applied for other abdominal pathologies.

This study examines and compares attitudes of consumers who take advantage of rebate offers with those who have not used such deals. Specifically, consumer attitudes toward store attributes and shopping are examined. The findings suggest that rebate users are more price sensitive and less store loyal than non-users. They look for stores with frequent price promotions and seek information about such stores by monitoring retail advertisements. Planning and strategic issues for the retailer are discussed.

We report the results of a prospective, longitudinal quality of life survey on our adult right lobe (RL) liver donors. A total of 47 donors were enrolled; a standard SF-36 form and 43 questions developed by our team were completed before donation, at 1 week, and 1, 3, 6 and 12 months after donation. There were no donor deaths. Twenty-nine complications occurred in 16 patients. Major complication rate was 12.8%. Employment status and personal finances were identified as major stressors. All donors who wished to return to work did so by 1 year (mean 3.4 months). Individuals reported between 0 dollars and 25,000 dollars in losses (wages, travel, lodging, etc.). Relationships with recipients and other family members were not altered significantly. Anticipated pain (predonation) was greater than actual pain reported. Donors indicated satisfaction with the donation process regardless of recipient outcome. Physical complaints were significant at 1 week and 1 month, but returned to baseline. Donor mental health remained stable. In conclusion, RL donors found the experience to be a positive one throughout the first postdonation year. The study identified areas (finances, employment and expected recipient outcomes) to be stressed as future donors are evaluated.

Extrahepatic portal vein thrombosis (EHPVT) may occur in children or adults and usually comes to clinical attention due to complications of portal hypertension such as variceal hemorrhage. A variety of standard surgical techniques exist to manage these patients, but when these fail surgical options are limited. We describe two novel portosystemic shunts that utilize the gonadal vein as an autologous conduit. Four patients were evaluated for EHPVT with variceal bleeding. None of the patients were candidates for a standard splenorenal shunt due to prior surgical procedures. The first patient underwent a left mesogonadal shunt and the remaining 3 patients underwent a right mesogonadal shunt. Postoperative ultrasound or computed tomography (CT) scan confirmed early patency of the shunt in each patient. There have been no further episodes of variceal hemorrhage with follow-up of 3.5 years in the child who underwent the left mesogonadal shunt, and 17, 19, and 20 months in the patients who underwent the right mesogonadal shunt. Three of the 4 shunts remain patent. One shunt thrombosis occurred in a patient homozygous for the Factor V Leiden mutation despite anticoagulation with coumadin. This is the first report of the successful use of the gonadal vein as an in situ conduit for constructing a portosystemic shunt. In conclusion, the right and left mesogonadal shunts may be useful as salvage operations for patients with EHPVT who have failed standard surgical shunt procedures.

Severe macrosteatosis in the donor liver is considered a major predictive factor of primary graft non-function. Such livers are usually discarded despite an ever-growing need for donor livers. We report our recent experience in a patient (#1) who had an excellent outcome following liver transplantation (LT) of a 65–70% macrosteatotic graft and compare his findings with those of two other (#2 and #3) recipients of moderate to severe macrosteatotic grafts. Both patients (#2 and #3) had initial diminished function, with recovery in patient #2 but delayed graft non-function requiring re-LT (day 24) in patient #3. Patient #1 had no intra-operative complications, while patient #2 had mild complications due to prior adhesions and graft capsular laceration. In patient #3, extensive intra-abdominal adhesions resulting in excessive bleeding occurred during recipient hepatectomy. Total ischemic times: 2.48, 6.10, and 8.18 h; total blood product usage: 43, 81, and 223 units; post-LT hospital stay: 9, 21, and 69 days were seen in patients #1, #2 and #3, respectively. In conclusion, post-LT excellent graft function was seen in one recipient of 65–70% macrosteatotic graft. Transplantation of grafts with moderate/severe macrosteatosis may be inadvisable in patients with extensive intra-abdominal adhesions with expectant excessive bleeding and long ischemia times.

A retrospective analysis of 51 primary sclerosing cholangitis (PSC) patients who underwent liver transplant (LT) identified 16 with xanthogranulomatous cholangiopathy (XGC) at the native liver hilum. Pre-LT clinical and laboratory data and post-LT course and outcome of patients with XGC were compared with the 35 PSC patients without XGC. The XGC and non-XGC groups were similar with respect to age and laboratory data at the time of LT. Pre-LT cholecystectomy was performed in 44% versus 26% and biliary bypass procedure in 38% versus 26% of patients with and without XGC, respectively (P = NS). Peri-operative complications resulted in six (38%) deaths or retransplantation within 60 days of LT in the XGC group compared with 4 (11%) in the non-XGC group (P = .05). Patient survival at 60 and 100 days post-LT was better in the non-XGC group (P = .01). The causes of death or retransplantation within 60 days post-LT in the patients with XGC included primary nongraft function (1), uncontrolled bleeding (3), and sepsis (2), while in the non-XGC group these were uncontrolled bleeding (2), sepsis (1), and primary nongraft function (1). Mean graft survival ± SD was 1,081 ± 1,584 days in patients with XGC versus 2,149 ± 1,679 days in patients without XGC. The presence of XGC in the native liver hilum of PSC patients undergoing LT was associated with a higher rate of early post-LT mortality or retransplantation. In conclusion, no pre-LT clinical features or laboratory tests were identified that predicted the presence of XGC in PSC patients. (Liver Transpl 2004;10:115–122.)

Although recurrent primary biliary cirrhosis (PBC) after liver transplantation (LT) has been reported, the full spectrum of changes and progression to fibrosis and cirrhosis is not yet established. We performed a detailed retrospective clinicopathologic analysis of 43 patients who underwent LT for PBC. Eight patients (18.6%) had definite recurrent PBC with florid duct lesions, 5 patients (11.6%) had recurrence with features of autoimmune liver disease, not otherwise specified (AILD-NOS), 7 patients (16.3%) had plasmacytosis only, 4 patients (9.3%) had chronic rejection, 18 patients (41.9%) have no recurrence at present, and 1 patient (2.3%) had acquired hepatitis C. Although definite diagnoses of PBC and AILD-NOS recurrences (n = 13) were made 1 month to 14 years (median, 4 years) post-LT, all patients had plasmacytosis in their earlier biopsy specimens. Also, these patients showed similar pre-LT and post-LT clinical features, with progressive fibrosis in 4 of 8 and 2 of 5 patients, respectively. Four of 13 patients with definite recurrence and 14 of 18 patients with no recurrence were administered azathioprine (AZA) as part of their post-LT therapy (P =.01). Six of 13 and 16 of 18 patients currently are alive, with median follow-ups of 11 and 5 years, respectively. No significant differences were seen with donor-recipient group A, group B, group O blood type, sex, or HLA mismatches; native liver histological characteristics; or tacrolimus-based therapy. In conclusion, recurrent autoimmune liver disease was seen in 30% of patients after LT for PBC and had features of PBC and/or AILD-NOS. Progression seen in 46% of patients was associated with late graft failure. Patients with no recurrent disease had shorter follow-up periods and more frequent immunosuppression, including AZA; some may still develop recurrence with longer follow-up.

The incidence of cryptogenic cirrhosis (CC) has decreased since the discovery of hepatitis C virus (HCV), still the etiology in 5% of cases with cirrhosis remains unresolved. Our aims were to define the clinicopathologic features of CC at liver transplantation (LT), evaluate the post-LT course with outcome and define the possible pathogenetic mechanisms. 27/534 LT recipients (5%) over a period of 16.5 years were entered in the LT database as cases of CC. A detailed analysis of pre- and post-LT clinical and all liver pathology specimens was performed. Based on clinicopathologic findings, a more definite diagnosis was possible in 23 of 27 (85%): Nonalcoholic steatohepatitis (NASH) in 9 (33%), autoimmune liver disease (AILD) in 6 (22%), alcoholic liver disease in 4, secondary biliary cirrhosis in 2 and 1 each of hepatitis C and portal venopathy. 4/27 cases remained unresolved. In the NASH group, native livers had focal steatosis, Mallory's hyalin, glycogenated hepatocytic nuclei, high-grade inflammation, and 3+ bile duct proliferation. Large cell dysplasia was more common in this group compared to other patients. Two patients had recurrence of NASH after LT. In AILD group native livers had little or no bile duct proliferation. Two patients had recurrence in AILD group. Of 27 patients 19 are alive (70%) with a follow-up of 407-3647 days. Based on the study results, the following conclusions were reached: (1) CC results from varying etiologies, which can be defined by a careful clinicopathologic analysis in a majority (85%) of cases; (2) Nonalcoholic steatohepatitis (33%) and AILD (22%) are the common underlying causes of CC; and (3) Post-LT outcome for CC is disease dependent with, recurrent disease seen in both nonalcoholic steatohepatitis (22%) and autoimmune liver disease (33%).

Measures of store images play an important role in both applied and basic marketing research. Marketing managers utilize measures of store image (and product images) to help develop and test competitive strategies. This paper evaluates prior image research efforts in terms of conceptualization of retail image, dimensions of image, and methodologies used in measuring image. It looks at environmental changes and their impact upon image and suggests priorities for future research in retail image.

Although advertising by professionals may not become the next major marketing phenomenon, it has increased steadily over the past several years and is becoming increasingly common. In the climate of competitiveness that professionals will inhabit in the 1980s, there will be many opportunities for communications and marketing professionals and for advertising agencies to serve the professions. This paper reviews the literature and takes the position that professional communication and advertising skills can play a major and creative role in giving the public a clearer understanding of the individual professions. At the same time they can help individual firms profit and grow.

Post[ndash ]orthotopic liver transplantation (OLT) recurrence of hepatitis C is virtually universal, but histological progression of disease is not. This study examines long-term clinical and liver histological features at and after OLT to elucidate factors predictive of hepatitis C recurrence and progression after OLT. A blinded retrospective review of clinical, serological, and histopathologic features of 65 patients who underwent OLT for hepatitis C and Non A Non B hepatitis was conducted. Histological findings of recurrent hepatitis C and progression (fibrosis, [ge ] grade 2 by last follow-up) were correlated with clinical parameters. Histological recurrence of hepatitis C was seen in 43 of 65 patients, with progression in 19 patients. Histological findings in the native liver and post-OLT biopsy specimen at the time of recurrence showed no correlation with hepatitis C recurrence and progression. Patients treated with azathioprine (AZA)-containing immunosuppressive regimens experienced less recurrence (6 of 17 v 37 of 48 patients; P [lt ] .005) and progression (1 of 17 v 18 of 48 patients; P = .014) than those without AZA as part of their immunosuppressive regimen. No difference was seen between patients treated with cyclosporine versus those administered FK506 ( P [gt ] .05). Histological recurrence of hepatitis C after OLT is seen in 66% of patients with progressive disease and 29% of all patients. The grade of inflammation in the native liver at the time of OLT and time of recurrence is not predictive of progression. AZA-containing regimens reduce histological recurrence and progression of hepatitis C in post-OLT patients. ( Liver Transpl 2001;7:1056-1063. )

Life-threatening hypophosphatemia (phosphorus < 1.0 mg/dL) has been reported only once after liver resection for tumor and was associated with a significant increase in postoperative complications. Hypophosphatemia is associated with reversible cardiac dysfunction, hypoventilation, and impaired immunity. The purpose of this study was to determine the incidence of hypophosphatemia after elective right hepatic lobectomy for live donor adult liver transplantation (LDALT), investigate the associated complication rate and surgical outcome of live liver donors, and determine the efficacy of prospective treatment with phosphate repletion as part of total parenteral nutrition (TPN). Evaluation of 30 donors who provided 30 right-lobe grafts between December 1998 and January 2000 was performed. Of the initial 18 live liver donors (group 1), 10 donors were treated with TPN that contained slightly more (35 ± 8 mmol/d) than the recommended daily allowance (RDA) of phosphorus (30 mmol/d) starting on postoperative day 1. The last 12 donors (group 2) were prospectively studied and administered similar TPN with 2 times the RDA for phosphorus (60 mmol/d). All donors in group 1 developed hypophosphatemia that was either life threatening (phosphorus < 1.0 mg/dL) in 70% or severely depleted (phosphorus, 1.5 to 1.1 mg/dL) in 30%. With more aggressive phosphate repletion (group 2), only 8% developed life-threatening (phosphorus < 1.0 mg/dL) hypophosphatemia and 30% developed severe (phosphorus, 1.1 to 1.5 mg/dL) hypophosphatemia. Results suggest that hypophosphatemia is a universal event after LDALT and may have contributed to the observed complications in this study. Repletion of phosphorus at twice the RDA abrogates the incidence of hypophosphatemia and may reduce donor morbidity. Institutions performing LDALT should carefully monitor live liver donors for hypophosphatemia and correct abnormal phosphate levels. Additional studies are needed to determine whether more aggressive parenteral repletion can prevent postoperative hypophosphatemia and thus improve outcomes. (Liver Transpl 2001;7:637-642.)

Liver allocation remains problematic because current policy prioritizes status 2B or 3 patients by waiting time rather than medical urgency. On February 21, 2000, we implemented a variance to the United Network for Organ Sharing liver allocation policy that redefined status 2A by much more rigid, definable criteria and prioritized status 2B patients by using a continuous medical urgency score based on the Child-Turcotte-Pugh score and other medical conditions. In this system, waiting time is used only to differentiate status 2B candidates with equal medical urgency scores. Comparing the 6-month period (period 1; n = 67) before implementation of this system to the 6-month period after implementation (period 2; n = 75), there was a significant reduction in the number of transplantations performed for patients listed as status 2A (46.3% to 14.7%; P = .002) and an increase in the number of patients listed as status 2B who received transplants (44.8% to 70.7%; P = .10). Most dramatically, there was a 37.1% reduction in overall deaths on the waiting list from 94 deaths in period 1 to 62 deaths in period 2 ( P = .005), with the most significant reduction for patients removed from this list at status 2B (52 v 18 patients; P = .04). There were 3 postoperative deaths in each period, with only 1 graft lost in period 2. Status 2B patients with the greatest degree of medical urgency received transplants without multiple peer reviews requesting elevation to 2A status. We conclude that a continuous medical urgency score system allocates donor livers much more fairly to those in medical need and reduces waiting list mortality without sacrificing efficacy.( Liver Transpl 2001;7:173-178 .)

McGuire MM, Jones BA, Hull MA, Misra MV, Smithers CJ, Feins NR, Jenkins RL, Lillehei CW, Harmon WE, Jonas MM, Kim HB. Combined en bloc liver–double kidney transplantation in an infant with IVC thrombosis. Pediatr Transplantation 2011: 15: E142–E144. © 2010 John Wiley & Sons A/S. Abstract: We report a case of a pediatric en bloc liver-double kidney transplant in a patient with IVC thrombosis below the renal veins. The patient is an 11-month-old girl diagnosed with congenital nephrotic syndrome at two months of age. Multifocal liver masses were identified on routine ultrasound at eight months of age. Alpha fetoprotein level was 55 319. Biopsy confirmed hepatoblastoma. CT scan confirmed multiple lesions in both lobes, which would require liver transplantation for resection. She was also found to have thrombosis of her infrarenal IVC secondary to multiple central lines. She was listed for combined liver–kidney transplant and began chemotherapy. After four cycles of chemotherapy, she underwent bilateral nephrectomies followed by a combined en bloc liver-double kidney transplant from a size matched donor. In order to provide adequate venous outflow from the kidneys in the absence of a recipient infrarenal IVC, the donor liver and kidneys were procured en bloc with a common arterial inflow via the infrarenal aorta and common outflow via the suprahepatic IVC. Kidney transplantation in the absence of adequate recipient venous drainage may require unusual vascular reconstruction techniques. This case demonstrates a novel approach in patients who may require combined liver–kidney transplantation.

The purpose of this study was to identify the significance and clinical correlation of steatosis in donor and posttransplantation liver biopsies. One hundred twenty-six liver biopsies with fatty change from 86 liver transplant patients were reviewed. Micro- and macro-steatosis were graded semiquantitatively and correlated with clinical and other pathologic parameters. Fifty-one donor biopsy specimens, from 50 patients, had combinations of micro- (predominantly) and macro-steatosis. One of 2 patients with high-grade micro- and macro-steatosis required a retransplantation on the third day. Three early deaths were not related to graft dysfunction. In 36 patients, steatosis developed after transplantation. In 13 of 36, steatosis was seen in the early postoperative period with a background of severe ischemic injury, 6 of whom died within 45 days posttransplantation. Other causes of steatosis developing after liver transplantation included hepatitis C (n = 12), alcoholic steatohepatitis (n = 3), diabetes mellitus or obesity (n = 7) and poor nutrition (n = 2). The presence of steatosis in 1 patient's donor and all posttransplantation biopsy specimens remained unexplained. In conclusion, (1) microsteatosis in donor liver biopsy specimens has no effect on graft function; (2) ischemic injury with development of steatosis in the early posttransplantation period may be associated with poor clinical outcome; and (3) steatosis in the posttransplantation period is uncommon and usually related to recurrent or acquired hepatitis C.

Although recurrence of viral hepatitis in liver transplants is common, data comparing recurrent hepatitis B (HB), hepatitis C (HC), and co-existing dual hepatitis B and C (HBC) are sparse. Posttransplantation liver biopsies, along with molecular, serological, immunohistochemical, and clinical data from 27 patients with pretransplantation diagnosis of chronic viral hepatitis, were reviewed. The patients were placed into 4 groups: Group I, with pretransplantation HB (n = 8); group II, with pretransplantation HC (n = 10); group III with pretransplantation HC and anti-HB surface or core antibody (n = 4); and group IV, with pretransplantation HBC (n = 5). The histopathologic findings and patient outcome were compared in the 4 groups. A high rate of recurrence of viral hepatitis was seen for all 4 groups: Group I = 100%, group II = 90%, Group III = 100%, and group IV = 80%, with the mean (median) recurrence time of 308 (224), 82 (52), 61 (64), and 125 (70) days, respectively. The number of deaths (their median survival times) were: group I = 4 (374 days), group II = 4 (794 days), group III = 1 (1,143 days), and group IV = 5 (448 days). The earliest histological findings of lobular injury was the presence of acidophil bodies and Kupffer cell hyperplasia, the latter being more prominent in recurrent HC cases. Recurrent HB presented in 2 forms: early (before 150 days) with poor survival and with either severe necroinflammatory histology or with features of fibrosing cholestatic hepatitis, and delayed (after 150 days), with mild necro-inflammatory activity and prolonged survival. HC with or without anti-HB antibodies had early recurrence, but the course was slowly progressive. Patients with HBC had recurrence of both viruses; however, the course was dictated by HB virus.

Patients on cardiac assist devices are often considered to be high-risk solid organ donors. We report the first case of a reduced size liver transplant performed using the left lateral segment of a pediatric donor whose cardiac function was supported by a Berlin Heart. The recipient was a 22-day-old boy with neonatal hemochromatosis who developed fulminant liver failure shortly after birth. The transplant was complicated by mild delayed graft function, which required delayed biliary reconstruction and abdominal wall closure, as well as a bile leak. However, the graft function improved quickly over the first week and the patient was discharged home with normal liver function 8 weeks after transplant. The presence of a cardiac assist device should not be considered an absolute contraindication for abdominal organ donation. Normal organ procurement procedures may require alteration due to the unusual technical obstacles that are encountered when the donor has a cardiac assist device.

The causes and pathologic changes leading to fibrosis and cirrhosis after orthotopic liver transplantation (OLT) are not fully defined. The computerized pathology files were searched for cases of fibrosis/cirrhosis after OLT. Of 493 grafts from 435 patients, 35 grafts from 32 patients of posttransplantation liver fibrosis/cirrhosis were identified and retrieved (7%). Detailed histopathologic examinations of all post-OLT liver biopsy specimens were performed in conjunction with clinical, virologic, serologic, and molecular diagnostics information. Two cases with subcapsular septa and fibrous tissue close to hilum were excluded as false positives. Fibrosis/cirrhosis was confirmed in the remaining 33 grafts. In 20, the underlying cause was recurrent viral hepatitis, including eight with hepatitis C, 10 with hepatitis B, and two with combined hepatitis C and B. Another two with pretransplantation chronic hepatitis B developed cirrhosis without detectable virologic markers after OLT; these were biliary type secondary to obstruction in one, and chronic changes due to severe graft ischemia in one. Three patients acquired hepatitis C after OLT, with molecular confirmation available in two. In five patients, the underlying causes were Budd-Chiari syndrome and autoimmune hepatitis, recurrent autoimmune hepatitis, recurrent primary biliary cirrhosis, alcohol-induced liver disease, and recurrent bile duct carcinoma. Three cases had centrilobular fibrosis but without bridging septa or cirrhosis as a result of chronic rejection. It was concluded that (1) Cirrhosis after OLT is uncommon (7%). (2) Chronic rejection does not lead to cirrhosis, but it may result in centrilobular fibrosis. (3) In most (70%) cases, cirrhosis after OLT is attributed to recurrent or acquired viral hepatitis.

Our purpose was to establish the earliest histologic parameters of acute hepatitis that correlated with recurrent hepatitis C virus (HCV) infection in liver allografts. Histologic reviews of posttransplant liver biopsies from eight patients with pretransplant chronic HCV (group I) and eight with pretransplant non-HCV liver disease (group II) were performed and correlated with concurrent or subsequent presence or absence of HCV-RNA by polymerase chain reaction (PCR). Six of eight group I patients developed HCV-RNA positivity in liver and serum. Of the histologic parameters studied, the presence of Kupffer cell hyperplasia, spotty hepatocellular necrosis (acidophil bodies), or both, correlated the most with the earliest diagnosis of acute recurrent hepatitis. The postoperative time period for the earliest diagnosis of recurrent HCV was variable (34 to 123 days). These early indicators and the time of their appearance were not predictive of the course of the disease process or the final outcome of the patient. The recurrence rate of HCV infection in liver allografts is high. The presence of Kupffer cell hyperplasia and diffusely scattered acidophil bodies are reliable, early histologic indicators of an acute hepatitic process.

Patients with renal failure after liver transplantation have a particularly poor prognosis. Therefore, in the setting of end-stage renal disease requiring dialysis or severe renal insufficiency that will not improve after liver replacement, combined liver-kidney transplantation (LKT) is the preferred approach. We have adopted a policy of LKT in patients with end-stage liver disease and renal insufficiency undergoing dialysis or with a creatinine clearance less than 35 mL/min and evidence of chronic renal dysfunction. Since 1991, we have performed 208 orthotopic liver transplantations. Fourteen patients (8%) have undergone combined LKT, including 6 patients undergoing hemodialysis. Cytotoxic cross-matches (modified Amos technique and antihuman globulin method) were performed on 13 of 14 patients and were positive in 3 patients. Two patients died less than 4 months after LKT and 12 patients are alive and well. Graft survival censored for patient death was 100% for liver allografts and 93% for renal allografts, with a mean follow-up of 39 +/- 24 months. The most recent serum creatinine level in the patients with the 11 functioning grafts was 1.1 +/- 0.6 mg/dL. Biopsy-proven acute rejection occurred in 50% of simultaneous liver allografts. By contrast, only a single episode (6%) of renal allograft dysfunction was attributable to acute rejection. All rejection episodes occurred in the first 90 days after transplantation and were steroid sensitive. Three of 14 combined procedures were performed in the setting of a positive cytotoxic cross-match. In 2 recent patients, the results were confirmed by positive cross-matches to the donor's T and B cells by flow cytometry. Flow cytometric cross-matches reverted to negative 1 hour after liver transplantation and several hours before the administration of antithymocyte globulin. The cross-matches remained negative on postoperative days 1 and 7. Presently, all 3 patients with a positive cross-match enjoy normal hepatic and renal function at 631, 706, and 2275 days follow-up. Renal scans were performed in 4 LKT recipients not previously undergoing hemodialysis and indicated varying and unpredictable degrees of function in the native and transplanted kidneys. In conclusion, combined LKT can be performed safely and is associated with a low rate of acute rejection, even in the setting of a positive cross-match. Predicting which patients with renal insufficiency will benefit from LKT remains challenging; however, these results suggest that LKT should be encouraged in patients with evidence of irreversible renal insufficiency who require liver transplantation.

BACKGROUND Unresectable adenocarcinoma of the biliary tree are associated with a very poor prognosis. 5-fluorouracil (5-FU) combination regimens have produced objective response rates in approximately 10-20% of patients. Leucovorin increases the selective cytotoxicity of 5-FU. There also are encouraging reports of carboplatin in combination with 5-FU in other gastrointestinal tract malignancies. METHODS Fourteen consecutive eligible patients were treated with a combination of carboplatin, 300 mg/m2, intravenously (i.v.) on Day 1 only and 5-FU, 400 mg/m2, i.v. with leucovorin, 25 mg/m2, i.v. on Days 1-4. All patients were required to have a histologically confirmed diagnosis and measurable disease. Patients were evaluated for response, survival, and toxicity. RESULTS A total of 48 cycles of therapy were delivered. The median survival was 5 months. One patient achieved complete remission and two others partial remission, for a total response rate of 21.4%. Four additional patients had stable disease for a median duration of 4 months. The therapy was well tolerated, with moderate myelosuppression as the main dose-limiting toxicity. CONCLUSIONS The current combination regimen of leucovorin-modulated 5-FU with carboplatin is well tolerated with appropriate supportive care, produces significant objective responses in 21% of patients with biliary tree carcinoma, and should be considered for the treatment of this disease. Cancer 1998;82:2321-2325. © 1998 American Cancer Society.

Background Liver disease is associated with impaired metabolism of these amino acids phenylalanine and tyrosine. Decreased metabolism of these amino acids leads to abnormal plasma elevations and impaired clearance rates. We have developed a noninvasive breath test that measures hepatic cytosolic enzyme activity. Methods The rate of hepatic phenylalanine metabolism was quantitatively calculated from the appearance of 13 CO 2 in the breath using the non-radioactive tracer L-[1- 13 C]phenylalanine. Results Normal controls (n = 47) oxidized phenylalanine more than twice that of end-stage liver disease patients (n = 117). Significant differences in the percent of phenylalanine oxidized per hour (mean ± SEM) were found between controls (7.08% ± 0.33%, 95% Cl: 6.42%–7.74%) and Child Pugh classification patients, class A (4.96% ± 0.69%, 95% Cl: 3.50%–6.42%), class B (2.88% ± 0.13, 95% Cl: 2.39%–3.38%) and class C (1.75% ± 0.13, 95% Cl: 1.50%–2.01%). The phenylalanine breath test score significantly correlated with albumin levels, prothrombin time and total bilirubin. Conclusion We have demonstrated that phenylalanine oxidation is significantly decreased with end-stage liver disease and is correlated with the best clinical measures of liver disease.

Epoxyeicosatrienoic acids (EETs), lipid mediators produced by cytochrome P450 epoxygenases, regulate inflammation, angiogenesis, and vascular tone. Despite pleiotropic effects on cells, the role of these epoxyeicosanoids in normal organ and tissue regeneration remains unknown. EETs are produced predominantly in the endothelium. Normal organ and tissue regeneration require an active paracrine role of the microvascular endothelium, which in turn depends on angiogenic growth factors. Thus, we hypothesize that endothelial cells stimulate organ and tissue regeneration via production of bioactive EETs. To determine whether endothelial-derived EETs affect physiologic tissue growth in vivo, we used genetic and pharmacological tools to manipulate endogenous EET levels. We show that endothelial-derived EETs play a critical role in accelerating tissue growth in vivo, including liver regeneration, kidney compensatory growth, lung compensatory growth, wound healing, corneal neovascularization, and retinal vascularization. Administration of synthetic EETs recapitulated these results, whereas lowering EET levels, either genetically or pharmacologically, delayed tissue regeneration, demonstrating that pharmacological modulation of EETs can affect normal organ and tissue growth. We also show that soluble epoxide hydrolase inhibitors, which elevate endogenous EET levels, promote liver and lung regeneration. Thus, our observations indicate a central role for EETs in organ and tissue regeneration and their contribution to tissue homeostasis.

To evaluate breath-hold magnetic resonance (MR) imaging with single-shot and multishot T2-weighted fast spin-echo (SE) and inversion-recovery (IR) SE echo-planar (EP) SE (IR-SE-EP) sequences compared with conventional T2-weighted SE imaging for detection of liver masses.Imaging with all sequences was performed in 32 patients on a 1.5-T whole-body system. Images were compared on the basis of lesion-to-liver contrast-to-noise ratio (C/N), lesion conspicuity, and image quality. Image analysis was performed by two experienced radiologists in consensus.Lesion-to-liver C/Ns were highest on fat-suppressed-half-Fourier-single-shot-fast-SE images. For solid lesions, the lesion-to-liver C/Ns were highest with IR-fast-SE, which was significantly better (P.05) than IR-SE-EP and conventional SE techniques and also produced the best image quality. Sensitivity with IR-fast-SE was 96%; with fat-suppressed-half-Fourier-single-shot-fast-SE, 92%; with fat-suppressed-fast-SE, 89%; with IR-SE-EP, 83%; and with conventional SE, 78%.T2-weighted breath-hold imaging, particularly IR-fast-SE imaging, was more sensitive for hepatic masses than conventional SE imaging, with a substantial reduction in acquisition time. Half-Fourier-single-shot-fast-SE imaging was especially useful in patients who were unable to hold their breath.

BACKGROUND The purpose of this study was to investigate prognostic factors at presentation and the survival of North American patients with hepatocellular carcinoma (HCC). METHODS A retrospective analysis of medical records was performed for 314 patients identified through the Tumor Registry as having been evaluated for hepatocellular carcinoma at the Deaconess Hospital, Boston, Massachusetts, from 1986 through 1995. Clinical characteristics were noted, including age, sex, TNM staging, serum biochemistries, serum alpha-fetoprotein (AFP), patency of portal vasculature, cirrhosis, history of alcohol abuse, hepatitis-B or C positivity, hemochromatosis, treatment received, and ultimate survival from the date of diagnosis. RESULTS Overall median survival was 10 months. The presence of cirrhosis, a history of alcohol abuse, low albumin, high bilirubin, abnormal AFP, and portal vein obstruction (PVO) were each associated with significantly shorter survival, as was advanced stage. Only albumin, AFP, and PVO were independent risk factors by multiple regression analysis. Patients undergoing surgery had the longest median survival (45 months), followed by those receiving chemoembolization (14 months). Those patients who were untreated or received systemic chemotherapy alone had significantly shorter survivals (2-4 months). CONCLUSIONS Despite the difference in the underlying etiology of HCC in this population compared with Asian patients, poor prognostic indicators are similar. In this large series of patients at a single Northeastern hospital, analysis of presenting clinical characteristics was found to offer useful prognostic information. Cancer 1996;77:2217-22.

The effect of nifedipine on renal function in liver transplant recipients who were receiving tacrolimus was evaluated between January 1992 and January 1996. Two groups of patients receiving tacrolimus were compared over a period of 1 year, one group comprising hypertensive patients who were receiving nifedipine, and the other comprising nonhypertensive patients not receiving nifedipine. The time from transplant to baseline was similar in all patients. Nifedipine significantly improved kidney function as indicated by a significant lowering of serum creatinine levels at 6 and 12 months. The observed positive impact of nifedipine on reducing the nephrotoxicity associated with tacrolimus in liver transplant recipients should be an important factor in selecting an agent to treat hypertension in this population.

Livers from donors > or = 60 years of age are often considered inadequate for transplantation by many centers. With waiting times exceeding 1 year in our region, we have aggressively used livers from this donor age group. Between 1990 and 1994, 209 patients received 223 liver grafts at our institution. Of these, 29 (13%) were from donors > or = 60 years of age (group A) and 194 (87%) were from donors < 60 years of age (group B). The two groups were matched for recipient diagnosis and severity of disease. Group A and B donors had similar liver, renal, and hematologic studies prior to donation. Weight, sex, race and vasopressor requirement were also similar. Postoperative alanine aminotransferase, aspartate aminotransferase,and prothrombin time were not significantly different over the first 10 postoperative days. Group A grafts were significantly more cholestatic than group B grafts on postoperative days 6-10. The retransplantation rate for primary graft nonfunction was not significantly different from group A (6.7%) and group B (3.4%; P=0.04). Patient and graft survival rates at 1 year were 58.6 % and 44.8% for group A and 79.2% and 74.5% for group B (P

Patients with adult polycystic liver disease and massive cystic replacement of the liver may present with severe debilitation and impairment of functional performance or, rarely, with signs of portal hypertension or hepatic dysfunction. In those patients incapacitated by severe hepatomegaly secondary to massive cystic replacement with predominantly small cysts (2 cm) without areas of parenchymal sparing, liver transplantation is a therapeutic option. Five patients with incapacitating symptoms from polycystic liver disease underwent liver transplantation as a final therapeutic procedure. Two patients had previous fenestration procedures without significant relief. All patients had radiographic evidence of concomitant polycystic kidney disease; two of these patients were dialysis-dependent at the time of liver transplantation. One patient underwent combined liver-kidney transplantation, whereas another received a six-antigen matched kidney transplant 64 months after liver transplantation. Four of five patients are alive 84, 39, 20, and 8 months after successful liver transplantation. All four have returned to normal functional status with complete resolution of symptoms. Liver transplantation is a suitable option for the patient with bilobar small cystic liver disease without areas of parenchymal sparing. However, only patients with severely compromised functional status should be offered this therapy. Concomitant renal evaluation is mandatory, and a knowledge of the natural history of this disease will aid in the decision of whether a combined liver-kidney transplantation is indicated.

Liver transplantation for patients requiring life-support results in the lowest survival and highest costs. A ten year (1983-1993) regional experience with liver transplantation for critically ill patients was undertaken to ascertain the fate of several subgroups of patients. Of the 828 liver transplants performed at six transplant centers within the region over this period, 168 (20%) were done in patients who met today's criteria for a United Network of Organ Sharing (UNOS) status 1 (emergency) liver transplant candidate. Recipients were classified according to chronicity of disease and transplant number (primary-acute, primary-chronic, reTx-acute, reTx-chronic). Overall one-year survival was 50% for all status 1 recipients. The primary-acute subgroup (n=63) experienced a 57% one-year survival compared with 50% for the primary-chronic (n=51) subgroup (P=0.07). Of the reTx-acute recipients (n=43), 44% were alive at one year in comparison with 20% for the reTx-chronic (n=11) group (P=0.18). There was no significant difference in survival for the following : transplant center, blood group compatibility with donors, age, preservation solution, or graft size. For patients retransplanted for acute reasons (primary graft nonfunction (PGNF) or hepatic artery thrombosis [HAT]), survival was significantly better if a second donor was found within 3 days of relisting (52% vs. 20% ; P=0.012). Over the study period progressively fewer donor organs came from outside the region. No strong survival-based argument can be made for separating, in allocation priority, acute and chronic disease patients facing the first transplant as a status 1 recipient. Clearly patients suffering from PGNF or HAT do far better if retransplanted within 3 days. Establishing an even higher status for recipients with PGNF, perhaps drawing from a supraregional donor pool, would allow surgeons to accept more marginal donors, thus potentially expanding the pool, without significantly compromising patient survival. Retransplantation of the recipient with a chronically failing graft who deteriorates to the point of needing life-support is nearly futile, and in today's health care climate, not an optimal use of scarce donor livers.

Steatosis is a common finding that is seen in patients with both chronic hepatitis C and alcoholic liver disease; however, the extent of involvement in the former is generally minimal to mild. We present 2 patients who underwent live donor liver transplantation for end-stage liver disease that was caused by chronic hepatitis C (genotype 3) and alcohol abuse. Both patients presented with liver allograft dysfunction, with liver biopsy findings of moderate to marked steatosis. Exclusion of a relapse of alcohol use required intense questioning of both the patients and their families. A definitive diagnosis of recurrent hepatitis C was established by viral markers with institution of the proper therapy and resolution of graft dysfunction. We conclude that recurrent hepatitis C, particularly genotype 3, may present with severe steatosis. Recognition of this phenomenon is important, and confirmation with viral markers is necessary to provide optimal patient care.