John A. Donovan

Risk Factors for Graft Survival After Liver Transplantation from Donation After Cardiac Death Donors: An Analysis of OPTN/UNOS Data

Due to increasing use of allografts from donation after cardiac death (DCD) donors, we evaluated DCD liver transplants and impact of recipient and donor factors on graft survival. Liver transplants from DCD donors reported to UNOS were analyzed against donation after brain death (DBD) donor liver transplants performed between 1996 and 2003. We defined a recipient cumulative relative risk (RCRR) using significant risk factors identified from a Cox regression analysis: age; medical condition at transplantation; regraft status; dialysis received and serum creatinine. Graft survival from DCD donors (71% at 1 year and 60% at 3 years) were significantly inferior to DBD donors (80% at 1 year and 72% at 3 years, p < 0.001). Low‐risk recipients (RCRR ≤ 1.5) with low‐risk DCD livers (DWIT < 30 min and CIT < 10 h, n = 226) achieved graft survival rates (81% and 67% at 1 and 3 years, respectively) not significantly different from recipients with DBD allografts (80% and 72% at 1 and 3 years, respectively, log‐rank p = 0.23). Liver allografts from DCD donors may be used to increase the cadaveric donor pool, with favorable graft survival rates achieved when low‐risk grafts are transplanted in a low‐risk setting. Whether transplantation of these organs in low‐risk recipients provides a survival benefit compared to the waiting list is unknown.

Retransplantation for Hepatitis C: Results of a U.S. Multicenter Retransplant Study

It is widely perceived that outcomes are relatively poor following retransplantation (reTX) for recurrent of hepatitis C virus (HCV) infection. Transplant centers debate the utility of offering another liver to these patients. A U.S. study group was formed to retrospectively compare survival after reTX in patients with recurrent HCV (histologically proven) and those transplanted for other indications greater than 90 days after first transplantation, from 1996 to 2004. Patients were divided into 3 groups; group 1: HCV reTX (n = 43), group 2: non‐HCV reTX (n = 73), and group 3: recurrent HCV but no reTX (n = 156). They were predominantly male, Caucasian, with mean age of 47.2 yr. The commonest indications for non‐HCV reTX were chronic rejection (36%), hepatic artery thrombosis (31%) and recurrent primary sclerosing cholangitis (17%). Duration of hospitalization, number of intensive care unit (ICU) days, and time interval from listing to transplantation or reTX were similar between reTX groups. The 1‐yr and 3‐yr survival rates after reTX were also similar for HCV reTX and non‐HCV reTX groups (1 yr, 69% vs. 73%; 3 yr, 49% vs. 55%). Model for End‐Stage Liver Disease (MELD) scores were not predictive of survival from reTX. However, with a MELD score of >30 in the non HCV group, survival was <50%. In the recurrent HCV not undergoing reTX group, 30% were reevaluated for reTX but only 15% were listed for reTX and the 3‐yr survival was 47%. The most common reasons for not listing for reTX were recurrent HCV within 6 months (22%), fibrosing cholestatic hepatitis (19%), and renal dysfunction (9%). In conclusion, patients retransplanted for recurrent HCV had similar 1‐yr and 3‐yr survival when compared to patients undergoing reTX for other indications. MELD scores were not predictive of post‐reTX survival. Survival was <50% in the non‐HCV reTx group with MELD score of >30. Many patients with recurrent HCV are not considered for reTX and die from recurrent disease. Liver Transpl 13:1246–1253, 2007.

Live donor liver transplantation without blood products: strategies developed for Jehovah's Witnesses offer broad application.

Objective:Developing strategies for transfusion-free live donor liver transplantation in Jehovahs Witness patients. Summary Background Data:Liver transplantation is the standard of care for patients with end-stage liver disease. A disproportionate increase in transplant candidates and an allocation policy restructuring, favoring patients with advanced disease, have led to longer waiting time and increased medical acuity for transplant recipients. Consequently, Jehovahs Witness patients, who refuse blood product transfusion, are usually excluded from liver transplantation. We combined blood augmentation and conservation practices with live donor liver transplantation (LDLT) to accomplish successful LDLT in Jehovahs Witness patients without blood products. Our algorithm provides broad possibilities for blood conservation for all surgical patients. Methods:From September 1998 until June 2001, 38 LDLTs were performed at Keck USC School of Medicine: 8 in Jehovahs Witness patients (transfusion-free group) and 30 in non-Jehovahs Witness patients (transfusion-eligible group). All transfusion-free patients underwent preoperative blood augmentation with erythropoietin, intraoperative cell salvage, and acute normovolemic hemodilution. These techniques were used in only 7%, 80%, and 10%, respectively, in transfusion-eligible patients. Perioperative clinical data and outcomes were retrospectively reviewed. Data from both groups were statistically analyzed. Results:Preoperative liver disease severity was similar in both groups; however, transfusion-free patients had significantly higher hematocrit levels following erythropoietin augmentation. Operative time, blood loss, and postoperative hematocrits were similar in both groups. No blood products were used in transfusion-free patients while 80% of transfusion-eligible patients received a median of 4.5+/− 3.5 units of packed red cell. ICU and total hospital stay were similar in both groups. The survival rate was 100% in transfusion-free patients and 90% in transfusion-eligible patients. Conclusions:Timely LDLT can be done successfully without blood product transfusion in selected patients. Preoperative preparation, intraoperative cell salvage, and acute normovolemic hemodilution are essential. These techniques may be widely applied to all patients for several surgical procedures. Chronic blood product shortages, as well as the known and unknown risk of blood products, should serve as the driving force for development of transfusion-free technology.

A comparison of sirolimus vs. calcineurin inhibitor-based immunosuppressive therapies in liver transplantation

Background  Sirolimus is a potent immunosuppressive agent whose role in liver transplantation has not been well‐described.

Prolonged cholestasis associated with benazepril therapy.

tin in gastrointestinal carcinogenesis. In particular, we draw attention to the studies demonstrating that adiponectin promotes apoptosis and suppresses proliferation in a cell line of esophageal adenocarcinoma (6,7) . Moreover, a recently published study found that a single-nucleotide polymorphism in the adiponectin gene is associated with a decreased risk of esophageal adenocarcinoma, adjusting for obesity (8) . L at single-nucleotide polymorphism is also associated with higher circulating level of adiponectin (9,10) , further supporting the results of our study. We conclude from these K ndings that more research is needed to understand the etiologic and prognostic roles of adiponectin and other adipokines in the development of Barrett ’ s esophagus and progression to esophageal cancer.

Prediction of histologic alcoholic hepatitis based on clinical presentation limits the need for liver biopsy

The clinical presentation of alcoholic hepatitis (AH) can be mimicked by other alcoholic liver diseases. The aim of this study was to identify clinical features that predict AH on liver biopsy. Biopsies from patients hospitalized for presumed severe AH were used to identify a derivation cohort (101 patients) and validation cohort (71 patients). Using histologic scores for hepatocyte ballooning, Mallory‐Denk bodies, and lobular inflammation, 95 patient biopsies (55%) were classified as definite AH, 55 (32%) as possible AH, and 22 (13%) as no AH. Survival was similar among the groups, but mortality was significantly increased for patients with fatty change ≤50% on initial liver biopsy. An analysis limited to uninfected patients with definite AH or no AH in the derivation cohort identified a greater leukocyte count at admission and radiographic evidence of liver surface nodularity as independent predictors of definite AH on biopsy (P < 0.05). In the derivation cohort, the leukocyte count thresholds for ensuring 100% specificity for diagnosing definite AH were 10 × 109/L if the liver surface was nodular and 14 × 109/L if the liver surface was smooth, with a sensitivity of 76% and an area under the receiver operator characteristic curve of 0.88. In the validation cohort, these thresholds had a specificity of 86%, a sensitivity of 59%, and an area under the receiver operator characteristic curve of 0.72. Conclusion: The combination of an elevated leukocyte count and a nodular liver surface in the absence of active infection retrospectively identified patients with a high likelihood of histologic AH for whom liver biopsy may not be necessary. For patients with suspected severe AH who do not fulfill these criteria, liver biopsy is important to exclude other variants of alcoholic liver disease. (Hepatology Communications 2017;1:1070–1084)

Biliary Manifestations of Systemic Diseases

Patients with a variety of systemic diseases may present with clinical indications of biliary tract disorders. This article describes a group of systemic conditions associated with bile duct abnormalities and the role of endoscopic therapy in their diagnosis and management.