Retrospective analysis of long-term outcome 10 years after liver transplantation for Wilson disease: experience over three decades.

We evaluated long-term outcomes for patients with Wilson disease (WD) after liver transplantation (LT) and searched for risk factors for poor survival. Retrospective analysis of UNOS/OPTN data identified 156 pediatric and 515 adult cases of LT for WD between 1987 and 2016. Comparison cases were 10 442 pediatric and 104 874 adult non-WD transplant recipients. Survival was calculated using Kaplan-Meier analysis. Recipient, donor, and surgical variables were compared by Cox regression. Survival rates 3, 5, and 10 years after LT for adult WD patients (87.5%, 85.4%, and 80.5%, respectively) were significantly higher than those for non-WD patients (P < 0.001); survival rates for pediatric WD patients (90.5%, 89.7%, and 86.5%, respectively) did not differ significantly from non-WD patients. Graft survival in adult and pediatric patients followed similar trends. Regression analysis identified older age, female gender, and use of life support at the time of transplant as risk factors for decreased survival for adults with WD, and younger age, male gender, obesity, and high serum creatinine at the time of transplant as risk factors for poor survival in pediatric recipients with WD. Presentation with fulminant liver failure was not associated with survival in WD patients. No donor characteristic predicted poor survival. Long-term patient and graft survival after LT is excellent for both adult and pediatric WD patients.

Favorable Sustained Virologic Response Rates Using Direct-Acting Antiviral Therapies at a Large Safety-Net Hospital.

BACKGROUND: Direct-acting antivirals (DAA) have revolutionized the treatment of chronic hepatitis C virus (HCV) infection. OBJECTIVE: To evaluate the clinical effectiveness of DAA in a safety-net population. METHODS: Retrospective cohort study including patients who received at least one dose of DAA for chronic HCV infection. Primary outcome was sustained virologic response (SVR) defined as undetectable viral load at least 12 weeks after treatment termination. RESULTS: Notable patient (n=174) characteristics included: 58% racial/ethnic minority group members, 34% Medicaid or uninsured, and 51% cirrhosis. Overall, SVR was 87.4%, including 15 patients who were lost to follow-up and deemed treatment failures. Multivariate analysis significantly associated completion of therapy on time (OR 4.55, p=.009) and the presence of insurance (OR 7.25, p=0.008) with SVR. CONCLUSION: A favorable rate of SVR can be obtained in a safety-net population. The majority of treatment failure was due to patients being lost to follow-up.

Interferon-based hepatitis C therapy in a safety net hospital: access, efficacy, and safety.

AIMS: This study assesses the efficacy, accessibility, and safety of hepatitis C virus (HCV) treatment in a safety net hospital population. METHODS: Patients at Denver Health receiving pegylated interferon for HCV infection between 2008 and 2012 were included in this retrospective study. Sociodemographic, biochemical, and virologic data were collected on each patient. The primary outcomes were the rate of sustained virologic response and early treatment discontinuation, with reason for discontinuation documented. Multivariable analyses were performed to identify factors associated with the primary outcomes. RESULTS: Detectable HCV antibodies were found in 2912 patients, and 1630 had a detectable viral load. Eighty percent of these patients were uninsured/underinsured. Only 46% were seen in the hepatology clinic, and 8% received interferon-based HCV treatment. Of the 125 patients treated with interferon-containing regimens, 54% had genotype 1 infection. The overall rate of sustained virologic response (SVR) was 47%. Rapid virologic response, low FIB-4 score combined with age, and increasing number of days on therapy were associated with SVR in multivariable analysis. Therapy was prematurely discontinued in 43% of patients related to being lost to follow-up (30%), null response (24%), and intolerance to pegylated interferon/ribavirin (24%). Genotype 1 infection and unfavorable viral kinetics were associated with premature treatment discontinuation in multivariable analysis. There were no statistically significant associations between age, sex, ethnicity, race, diabetes, BMI, psychiatric comorbidities, income, employment status, homelessness, or insurance status and the primary outcomes. CONCLUSION: An acceptable SVR rate is achievable in a safety net patient population. Addressing the barriers to care will be paramount when using direct-acting antivirals.

Early weight changes after liver transplantation significantly impact patient and graft survival.

BACKGROUND AND AIM: Associations between pre-liver transplantation (pre-LT) BMI and post-LT survival are well described; however, there are few data assessing the associations between the commonly observed post-LT BMI changes and survival. We investigated the impact of early post-LT BMI change on post-LT patient and graft survival. METHODS: Using United Network for Organ Sharing data, we identified 2968 adult primary LT recipients who were not overweight pre-LT (BMI >16 to ≤25 kg/m), and who had BMI recorded at 2 years post-LT. Delta BMI was defined as the BMI difference between pre-LT and 2 years post LT. Recipients were grouped into three categories: BMI gain (increase by >1 BMI point), BMI loss (decrease by >1 BMI point), and BMI stable (maintained BMI within 1 point). Associations between delta BMI and patient and graft survival were evaluated using Kaplan-Meier and multivariable Cox regression analyses. RESULTS: BMI gain was common (54%) and associated with significantly greater 5-year patient and graft survival (90 and 89%, respectively), compared with recipients who had either BMI loss (77 and 74%, respectively, P<0.0001 for both) or were BMI stable (83%, P=0.04 and 82%, P=0.007, respectively). In multivariable analyses, increasing delta BMI was found to be inversely associated with risk for death and graft loss [hazard ratio 0.89 (95% confidence interval 0.86-0.91), P<0.001; and hazard ratio 0.88 (95% confidence interval 0.86-0.91), P<0.001, respectively]. CONCLUSION: This study of a large national liver transplant database demonstrated that post-LT BMI gain was associated with better patient and graft survival, whereas BMI loss was associated with reduced patient and graft survival.

Post-transplant survival is improved for hepatitis C recipients who are RNA negative at time of liver transplantation.

UNLABELLED: Hepatitis C virus (HCV) infection recurs universally in patients who are viremic at liver transplantation and likely accounts for the diminished post-transplant graft and patient survival. We evaluated whether undetectable HCV RNA pretransplant improves graft and patient survival after transplantation. Cases, defined by HCV listing diagnosis and positive HCV antibody, were selected from the Scientific Registry of Transplant Recipients database and further grouped as HCV RNA-positive (n = 4978) or negative (n = 445) based upon pretransplant testing. Controls were non-HCV recipients (n = 2995). RNA-negative cases had significantly better 5-year graft (72% vs. 64%) and patient (79% vs. 69%) survival than RNA-positive cases (P < 0.01 for both), and similar survival as controls (Graft: 72% vs. 74%, PATIENT: 79% vs. 80%; P > 0.05 for both). Nonproportional hazards modeling of RNA-positive cases identified a subgroup with rapid progression leading to early graft loss and death. Multivariable analyses confirmed that a positive HCV RNA prior to transplantation was a significant independent predictor of graft loss and death. In conclusion, HCV patients who have undetectable RNA at the time of liver transplantation experience improved long-term graft and patient outcomes. We speculate that the post-transplant survival of HCV recipients could be improved by safe and tolerable pretransplant antiviral strategies.

Risk of waitlist mortality in patients with primary sclerosing cholangitis and bacterial cholangitis.

Patients with primary sclerosing cholangitis (PSC) are at increased risk for bacterial cholangitis because of biliary strictures and bile stasis. A subset of PSC patients suffer from repeated episodes of bacterial cholangitis, which can lead to frequent hospitalizations and impaired quality of life. Although waitlist candidates with PSC and bacterial cholangitis frequently receive exception points and/or are referred for living donor transplantation, the impact of bacterial cholangitis on waitlist mortality is unknown. We performed a retrospective cohort study of all adult waitlist candidates with PSC who were listed for initial transplantation between February 27, 2002 and June 1, 2012 at the University of Pennsylvania and the University of Colorado-Denver. During this period, 171 PSC patients were waitlisted for initial transplantation. Before waitlisting, 38.6% (66/171) of the patients had a history of bacterial cholangitis, whereas 28.0% (44/157) of the patients with at least 1 Model for End-Stage Liver Disease update experienced cholangitis on the waitlist. During follow-up, 30 patients (17.5%) were removed from the waitlist for death or clinical deterioration, with 46.7% (14/30) developing cholangiocarcinoma. Overall, 12 of the 82 waitlist candidates (14.6%) who ever had an episode of cholangitis were removed for death or clinical deterioration, whereas 18 of the 89 candidates (20.2%) without cholangitis were removed (P = 0.34 for a comparison of the 2 groups). No patients were removed because of bacterial cholangitis. In multivariate competing-risk models, a history of bacterial cholangitis was not associated with an increased risk of waitlist removal for death or clinical deterioration (subhazard ratio = 0.67, 95% confidence interval = 0.65-0.70, P < 0.001). In summary, waitlist transplant candidates with PSC and bacterial cholangitis do not have an increased risk of waitlist mortality. The data call into question the systematic granting of exception points or referral for living donor transplantation due to a perceived risk of increased waitlist mortality.