Nigel Girgrah

Biliary Strictures in 130 Consecutive Right Lobe Living Donor Liver Transplant Recipients: Results of a Western Center

Biliary strictures remain the most challenging aspect of adult right lobe living donor liver transplantation (RLDLT). Between 04/2000 and 10/2005, 130 consecutive RLDLTs were performed in our center and followed prospectively. Median follow‐up was 23 months (range 3–67) and 1‐year graft and patient survival was 85% and 87%, respectively. Overall incidence of biliary leaks (n = 19) or strictures (n = 22) was 32% (41/128) in 33 patients (26%). A duct‐to‐duct (D‐D) or Roux‐en‐Y (R‐Y) anastomosis were performed equally (n = 64 each) with no difference in stricture rate (p = 0.31). The use of ductoplasty increased the number of grafts with a single duct for anastomosis and reduced the biliary complication rate compared to grafts ≥2 ducts (17% vs. 46%; p = 0.02). Independent risk factors for strictures included older donor age and previous history of a bile leak. All strictures were managed nonsurgically initially but four patients ultimately required conversion from D‐D to R‐Y. Ninety‐six percent (123/128) of patients are currently free of any biliary complications. D‐D anastomosis is safe after RLDLT and provides access for future endoscopic therapy in cases of leak or stricture. When presented with multiple bile ducts, ductoplasty should be considered to reduce the potential chance of stricture.

Antiviral treatment of recurrent hepatitis C after liver transplantation: predictors of response and long-term outcome.

Background. Efficacy and long-term outcome of antiviral therapy for recurrent hepatitis C after liver transplantation is poorly defined. Aim. This study aimed at assessing the efficacy of antiviral therapy regarding sustained hepatitis C virus (HCV) clearance, liver histology, and patient survival. Methods. We retrospectively reviewed all 446 patients who received a liver allograft at our institution for HCV-related cirrhosis between January 1992 and December 2006. Two hundred thirty-two patients (52%) were eligible for antiviral therapy based on predefined criteria (Metavir stage ≥1 and/or grade ≥2; protocol biopsies). One hundred seventy-two patients (39%) had no contraindication for treatment, received more than or equal to 1 dose of interferon-&agr;–based combination therapy, and form the basis of this analysis. Therapy was aimed for 48 weeks; median posttreatment follow-up was 68 months. Results. The overall sustained virological response (SVR) rate was 50% (genotype 1/4: 40%; genotype 2/3: 76%). SVR was higher on cyclosporine A (CsA) (56%) than on tacrolimus (44%, P=0.05), largely because of a lower relapse rate (6% vs. 19%, P=0.01). In multivariate analysis, genotype 2/3, CsA use, donor age, and pretreatment necroinflammatory activity were independently associated with SVR. SVR significantly improved histology and long-term survival (actuarial 5-year survival 96% vs. 69% in nonresponders, P<0.0001). Conclusion. Antiviral therapy of recurrent hepatitis C after liver transplantation is able to clear HCV in half the patients, more likely on CsA than on tacrolimus, and markedly improves outcome.

Management of chronic hepatitis C: Consensus guidelines

Since the last consensus conference on the management of chronic viral hepatitis, a number of studies looking at modifications of the standard course of treatment have been published. These changes have been sufficiently substantive to warrant review to determine whether any changes in the recommended treatment algorithms are needed. A consensus development conference was held in January 2007, and the present document highlights the results of the presentations and discussion about these issues. It reviews the epidemiology of hepatitis C in Canada, treatment of acute hepatitis C and new algorithms in chronic hepatitis C, including retreatment of previous treatment failures. In addition, sections on management of hepatitis C in special populations have been updated. There is also a section on the use of hematopoietic growth factors to help manage patients on therapy. The document should be read in conjunction with the previous document to identify changes. Some recommendations made in the previous document remain and are not discussed here.

Management of chronic hepatitis B: Consensus guidelines

The present document presents the proceedings of the consensus development conference on the management of viral hepatitis held in January 2007 under the auspices of the Canadian Association for the Study of the Liver and the Association of Medical Microbiology and Infectious Disease Canada. Several new agents have become available since the last such document was published in 2004, and new information has become available to help assess risk of adverse outcomes and who should be treated. In addition, the participants at the meeting identified a number of structural barriers that exist uniquely in Canada and that prevent physicians from properly managing their patients. The conference discussed the selection of patients for treatment and the drugs that can be used to treat these patients, as well as the treatment of hepatitis B in special populations. The present document should be read in conjunction with the companion document on the management of chronic hepatitis C.

Living-Donor Right Hepatectomy with or without Inclusion of Middle Hepatic Vein: Comparison of Morbidity and Outcome in 56 Patients

Venous congestion of segments V and VIII is observed frequently in living‐donor right lobe liver transplants without middle hepatic vein (MHV) drainage, and can be a cause of graft dysfunction and failure. Inclusion of the MHV with the graft is controversial, however, because of the perceived potential for increased donor morbidity.

Adult living liver donors have excellent long-term medical outcomes: the University of Toronto liver transplant experience.

Right lobe living donor liver transplantation is an effective treatment for selected individuals with end‐stage liver disease. Although 1 year donor morbidity and mortality have been reported, little is known about outcomes beyond 1 year. Our objective was to analyze the outcomes of the first 202 consecutive donors performed at our center with a minimum follow‐up of 12 months (range 12–96 months). All physical complications were prospectively recorded and categorized according to the modified Clavien classification system. Donors were seen by a dedicated family physician at 2 weeks, 1, 3 and 12 months postoperatively and yearly thereafter. The cohort included 108 males and 94 females (mean age 37.3 ± 11.5 years). Donor survival was 100%. A total of 39.6% of donors experienced a medical complication during the first year after surgery (21 Grade 1, 27 Grade 2, 32 Grade 3). After 1 year, three donors experienced a medical complication (1 Grade 1, 1 Grade 2, 1 Grade 3). All donors returned to predonation employment or studies although four donors (2%) experienced a psychiatric complication. This prospective study suggests that living liver donation can be performed safely without any serious late medical complications and suggests that long‐term follow‐up may contribute to favorable donor outcomes.

Analysis and outcomes of right lobe hepatectomy in 101 consecutive living donors.

The shortage of deceased organ donors has created a need for right lobe living donor liver transplantation (RLDLT) in adults. Concerns regarding donor safety, however, necessitate continuous assessment of donor acceptance criteria and documentation of donor morbidity. We report the outcomes of our first 101 donors who underwent right lobectomy between April 2000 and November 2004. The cohort comprised 58 men and 43 women with a median age of 37.8 years (range: 18.6–55 years); median follow‐up is 24 months. The middle hepatic vein (MHV) was taken with the graft in 55 donors. All complications were recorded prospectively and stratified by grade according to Claviens classification. Overall morbidity rate was 37%; all complications were either grade 1 or 2, and the majority occurred during the first 30 days after surgery. Removal of the MHV did not affect morbidity rate. There were significantly fewer complications in the later half of our experience. All donors are well and have returned to full activities. With careful donor selection and specialized patient care, low morbidity rates can be achieved after right hepatectomy for living donor liver transplantation.

The Difference in the Fibrosis Progression of Recurrent Hepatitis C After Live Donor Liver Transplantation Versus Deceased Donor Liver Transplantation Is Attributable to the Difference in Donor Age

Hepatitis C recurs universally after liver transplantation (LT). Whether its progression differs after live donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) is still debated. We retrospectively analyzed 201 consecutive LTs performed at our institution for hepatitis C–related end‐stage liver disease between April 2000 and December 2005 (46 LDLTs and 155 DDLTs). Patients were followed with protocol biopsies for medians of 29 (LDLT) and 39 months (DDLT; P = 0.7). Although overall graft and patient survival did not differ, the mean fibrosis stage (Metavir) was significantly higher at 12 to 48 months post‐LT (all P < 0.05), and the rate of fibrosis progression tended to be faster after DDLT than LDLT (0.19 versus 0.11 stage/year, P = 0.05). In univariate analysis, donor age, cold ischemic time, and DDLT were significantly associated with a fibrosis stage ≥ 1 at 1 year and a fibrosis stage of 3 or 4 at 2 years post‐LT. In multivariate analysis, however, donor age was the sole variable independently associated with both surrogate outcomes. Thus, donor age > 45 years carried a relative risk of 8.17 (confidence interval = 2.6–25.5, P = 0.001) for reaching fibrosis stage 3 or 4 at 2 years post‐LT. In conclusion, donor age, rather than the transplant approach, determines the progression of recurrent hepatitis C after LT. LDLT, allowing for the selection of younger donors, may particularly benefit hepatitis C patients. Liver Transpl 14:1778–1786, 2008.

Reduced Mortality with Right-Lobe Living Donor Compared to Deceased-Donor Liver Transplantation When Analyzed from the Time of Listing

Right lobe living donor liver transplantation (RLDLT) is not yet a fully accepted therapy for patients with end‐stage liver failure in the Western hemisphere because of concerns about donor safety and inferior recipient outcomes. An outcome analysis from the time of listing for all adult patients who were listed for liver transplantation (LT) at our center was performed. From 2000 to 2006, 1091 patients were listed for LT. One hundred fifty‐four patients (LRD; 14%) had suitable live donors and 153 (99%) underwent RLDLT. Of the remaining patients (DD/Waiting List; n = 937), 350 underwent deceased donor liver transplant (DDLT); 312 died or dropped off the waiting list; and 275 were still waiting at the time of this analysis. The LRD group had shorter mean waiting times (6.0 months vs. 9.8 months; p < 0.001). Although medical model for end‐stage liver disease (MELD) scores were similar at the time of listing, MELD scores at LT were significantly higher in the DD/Waiting List group (15.4 vs. 19.5; p = 0.002). Patients in Group 1 had a survival advantage with RLDLT from the time of listing (1‐year survival 90% vs. 80%; p < 0.001). To our knowledge, this is the first report to document a survival advantage at time of listing for RLDLT over DDLT.

Adverse cardiac events after orthotopic liver transplantation: A cross‐sectional study in 389 consecutive patients

Current American College of Cardiology/American Heart Association guidelines caution that preoperative noninvasive cardiac tests may have poor predictive value for detecting coronary artery disease in liver transplant candidates. The purpose of our study was to evaluate the role of clinical predictor variables for early and late cardiac morbidity and mortality and the predictive values of noninvasive cardiac tests for perioperative cardiac events in a high‐risk liver transplant population. In all, 389 adult recipients were retrospectively analyzed for a median follow‐up time of 3.4 years (range = 2.3‐4.4 years). Overall survival was 83%. During the first year after transplantation, cardiovascular morbidity and mortality rates were 15.2% and 2.8%. In patients who survived the first year, cardiovascular morbidity and mortality rates were 3.9% and 2%, with cardiovascular etiology as the third leading cause of death. Dobutamine stress echocardiography (DSE) and single‐photon emission computed tomography had respective sensitivities of 9% and 57%, specificities of 98% and 75%, positive predictive values of 33% and 28%, and negative predictive values of 89% and 91% for predicting early cardiac events. A rate blood pressure product less than 12,000 with DSE was associated with an increased risk for postoperative atrial fibrillation. Correspondence analysis identified a statistical association between nonalcoholic steatohepatitis/cryptogenic cirrhosis and postoperative myocardial ischemia. Logistic regression identified 3 risk factors for postoperative acute coronary syndrome: age, history of coronary artery disease, and pretransplant requirement for vasopressors. Multivariable analysis showed statistical associations of the Model for End‐Stage Liver Disease score and the development of acute kidney injury as risk factors for overall cardiac‐related mortality. These findings may help in identifying high‐risk patients and may lead to the development of better cardiac tests. Liver Transpl 21:13‐21, 2015.