Les Lilly

Health-state utilities and quality of life in hepatitis C patients

Abstract Objective Health-state utilities are global measurements of quality of life on a scale from 0 (death) to 1 (full health). Utilities are used to evaluate health outcomes and are the preferred outcome measure for policy models that determine the cost-effectiveness of treatments. Currently, utilities for hepatitis C virus (HCV)-infected patients have been estimated using expert judgments. The purpose of this study was to elicit HCV utilities directly from patients. Methods We assessed the utilities of 193 outpatients at various stages of chronic HCV progression by using a visual analog scale, the standard gamble technique, the Health Utilities Index Mark 3 survey, and the EuroQol Index survey. We also incorporated the nonutility-based Short Form-36v2 survey, which provides a detailed profile of health status. Results The mean standard gamble utilities were: 0.78 for patients without a recent liver biopsy and no signs of cirrhosis; 0.79 for mild to moderate chronic HCV infection; 0.80 for compensated cirrhosis; 0.60 for decompensated cirrhosis; 0.72 for hepatocellular carcinoma; 0.73 for transplant; and 0.86 for sustained virological responders to interferon ± ribavirin treatment. The Health Utilities Index Mark 3 survey and the EuroQol Index survey utilities were lower than Canadian population norms (p Conclusions These findings 1) suggest that quality of life (QOL) differences across the HCV clinical spectrum are smaller than previously believed; 2) support other evidence suggesting that QOL is significantly diminished in HCV patients; and 3) provide utility values derived directly from HCV patients.

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.

Improved Survival After Liver Transplantation in Patients with Hepatopulmonary Syndrome

Hepatopulmonary syndrome (HPS) is present in 10–32% of chronic liver disease patients, carries a poor prognosis and is treatable by liver transplantation (LT). Previous reports have shown high LT mortality in HPS and severe HPS (arterial oxygen (PaO2) ≤50 mmHg). We reviewed outcomes in HPS patients who received LT between 2002 and 2008 at two transplant centers supported by a dedicated HPS clinic. We assessed mortality, complications and gas exchange in 21 HPS patients (mean age 51 years, MELD score 14), including 11/21 (52%) with severe HPS and 5/21 (24%) with living donor LT (median follow‐up 20.2 months after LT). Overall mortality was 1/21 (5%); mortality in severe HPS was 1/11 (9%). Peritransplant hypoxemic respiratory failure occurred in 5/21 (24%), biliary complications in 8/21 (38%) and bleeding or vascular complications in 6/21 (29%). Oxygenation improved in all 19 patients in whom PaO2 or SaO2 were recorded. PaO2 increased from 52.2 ± 13.2 to 90.3 ± 11.5 mmHg (room air) (p < 0.0001) (12 patients); a higher baseline macroaggregated albumin shunt fraction predicted a lower rate of postoperative improvement (p = 0.045) (7 patients). Liver transplant survival in HPS and severe HPS was higher than previously demonstrated. Severity of HPS should not be the basis for transplant refusal.

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.

Liver Transplantation and Subsequent Risk of Cancer : Findings from a Canadian Cohort Study

Characterization of the long‐term cancer risks among liver transplant patients has been hampered by the paucity of sufficiently large cohorts. The increase over time in the number of liver transplants coupled with improved survival underscores the need to better understand associated long‐term health effects. This is a cohort study whose subjects were assembled with data from the population‐based Canadian Organ Replacement Registry. Analyses are based on 2034 patients who received a liver transplant between June 1983 and October 1998. Incident cases of cancer were identified through record linkage to the Canadian Cancer Registry. We compared site‐specific cancer incidence rates in the cohort and the general Canadian population by using the standardized incidence ratio (SIR). Stratified analyses were performed to examine variations in risk according to age at transplantation, sex, time since transplantation, and year of transplantation. Liver transplant recipients had cancer incidence rates that were 2.5 times higher than those of the general population [95% confidence interval (CI) = 2.1, 3.0]. The highest SIR was observed for non‐Hodgkins lymphoma (SIR = 20.8, 95% CI = 14.9, 28.3), whereas a statistically significant excess was observed for colorectal cancer (SIR = 2.6, 95% CI = 1.4, 4.4). Risks were more pronounced during the first year of follow‐up and among younger transplant patients. In conclusion, our findings indicate that liver transplant patients face increased risks of developing cancer with respect to the general population. Increased surveillance in this patient population, particularly in the first year following transplantation, and screening for colorectal cancer with modalities for which benefits are already well recognized should be pursued. Liver Transpl 14:1588–1597, 2008.

A graft to body weight ratio less than 0.8 does not exclude adult‐to‐adult right‐lobe living donor liver transplantation

Many centers require a minimal graft to body weight ratio (GBWR) ≥ 0.8 as an arbitrary threshold to proceed with right‐lobe living donor liver transplantation (RL‐LDLT), and there is often hesitancy about transplanting lower volume living donor (LD) liver grafts into sicker patients. The data supporting this dogma, based on the early experience with RL‐LDLT at Asian centers, are weak. To determine the effect of LD liver volume in the modern era, we investigated the impact of GBWR on the outcome of RL‐LDLT with a GBWR as low as 0.6 at the University of Toronto. Between April 2000 and September 2008, 271 adult‐to‐adult RL‐LDLT procedures and 614 deceased donor liver transplants were performed. Twenty‐two living donor liver transplantation (LDLT) cases with a GBWR of 0.59 to 0.79 (group A) were compared with 249 LDLT cases with a GBWR ≥ 0.8 (group B) and with 66 full‐graft deceased donor liver transplants (group C), who were matched 3:1 according to donor and recipient age, Model for End‐Stage Liver Disease score, and presence of hepatitis C and hepatocellular carcinoma with the low‐GBWR group. Portal vein shunts were not used. Markers of reperfusion injury [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], graft function (international normalized ratio and bilirubin), complications graded by the Clavien score, and graft and patient survival were compared. As expected, LD recipients had a significantly shorter cold ischemia time (94 ± 43 minutes for A, 96 ± 57 minutes for B, and 453 ± 152 minutes for C, P = 0.0001). However, the peak AST, peak ALT, absolute decrease in the international normalized ratio, day 7 bilirubin level, postoperative creatinine clearance, complication rate graded by the Clavien score, and median hospital stay were similar in all groups. The rate of biliary complications was higher with LD grafts than deceased donor grafts (19% for A versus 10% for B and 0% for C, P = 0.2). Patient survival was similar in all groups at 1, 3, and 5 years (91% for A versus 89% for B and 93% for C at 1 year, 87% for A versus 81% for B and 89% for C at 3 years, and 83% for A versus 81% for B and 87% for C at 5 years, P = 0.63). A Cox proportional regression analysis revealed only hepatitis C virus as a risk factor for poorer graft survival and not GBWR as a continuous or categorical variable. In conclusion, we found no evidence of inferior outcomes with smaller size grafts versus larger size LD grafts or full‐size deceased donor grafts. Further studies are warranted to examine the factors affecting the function of smaller grafts for living liver donation and thereby define the safe lower limits for transplantation. Liver Transpl 15:1776–1782, 2009.

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.

Recipient age affects long-term outcome and hepatitis C recurrence in old donor livers following transplantation.

We studied the role of donor and recipient age in transplantation/ischemia‐reperfusion injury (TIRI) and short‐ and long‐term graft and patient survival. Eight hundred twenty‐two patients underwent deceased donor liver transplantation, with 197 donors being ≥60 years old. We evaluated markers of reperfusion injury, graft function, and clinical outcomes as well as short‐ and long‐term graft and patient survival. Increased donor age was associated with more severe TIRI and decreased 3‐ and 5‐year graft survival (73% versus 85% and 72% versus 81%, P < 0.001) and patient survival (77% versus 88% and 77% versus 82%, P < 0.003). Hepatitis C virus (HCV) infection and recipient age were the only independent risk factors for graft and patient survival in patients receiving an older graft. In the HCV(+) cohort (297 patients), patients ≥ 50 years old who were transplanted with an older graft versus a younger graft had significantly decreased 3‐ and 5‐year graft survival (68% versus 83% and 64% versus 83%, P < 0.009). In contrast, HCV(+) patients < 50 years old had similar 3‐ and 5‐year graft survival if transplanted with either a young graft or an old graft (81% versus 82% and 81% versus 82%, P = 0.9). In conclusion, recipient age and HCV status affect the graft and patient survival of older livers. Combining older grafts with older recipients should be avoided, particularly in HCV(+) patients, whereas the effects of donor age can be minimized in younger recipients. Liver Transpl 15:1288–1295, 2009.