Faculty Bibliography

Frailty, a global impairment of multiple organ systems resulting in increased vulnerability to health stressors, is common in end-stage liver disease, multifactorial in etiology, and impacts overall mortality as well as outcomes in liver transplantation. This is a review of the currently available data, a synopsis of expert consensus, and a framework for transplant centers to approach frailty. We suggest that centers use a multidisciplinary team of healthcare providers and approach frailty in a programmatic fashion to provide effective patient care and ensure optimal transplant outcomes. The utilization of standardized protocols to address both malnutrition and physical debility is ideal and can help ensure safety. A toolbox of resources has been made available by experts in the field to facilitate this approach. The incorporation of new technology tailored to overcome barriers is another resource under investigation.

During the coronavirus 2019 pandemic we converted our liver transplant waitlist candidate education and support program to a virtual format and expanded it to include ongoing engagement sessions aimed to educate and empower patients to maximize opportunity for live donor liver transplantation. Over a period of 6 months from April 2020 to Sept 2020 we included 21 patients in this pilot quality improvement program. We collected data regarding patient response and potential donor referral activity. Overall, patient response was positive, and some patients saw progress toward live donor liver transplantation by fostering inquiry of potential live liver donors. Optimization of logistical aspects of the program including program flow, technology access, and utilization is required to enhance patient experience. Long-term follow-up is needed to assess impact on the outcome of transplantation rates. Future data collection and analysis should focus on assessment of any potential disparity that may result from utilization of virtual programming. Herein we provide a framework for this type of virtual program and describe our experience.

BACKGROUND:Fontan circulation alters portal venous hemodynamics, causing chronic passive hepatic congestion and fibrosis. This congestion increases liver stiffness (LS) leading to overestimates of liver fibrosis as measured by ultrasound shear wave elastography (SWE) of the liver. We evaluated whether Fontan circulation has a similar effect on spleen stiffness (SS) and SS/LS ratio as measured by SWE. METHODS:We retrospectively compared the SS of adult Fontan patients to age and gender matched, control patients without congenital heart disease. We correlated SS measurements to LS measurements and also performed a limited subgroup analysis of SS in Fontan patients with various manifestations of Fontan Associated Liver Disease. RESULTS:SS in Fontan patients was similar to healthy controls (1.43 vs. 1.36 m/s, p = 0.26). LS was elevated in 78% of the Fontan patients (mean 1.68 m/s, SD 0.31, 95% CI 1.53-1.85). The correlation between LS and SS was modest (Pearson's correlation coefficient, r = 0.5) but did not reach statistical significance (p = 0.06). The mean SS/LS ratio was 0.85 (95% CI 0.77-0.94). CONCLUSION:Based on our study cohort, SS in Fontan patients is similar to age and gender matched control patients without congenital heart disease. The SS/LS ratio, however, is frequently less than 1, which is lower than that reported in both healthy patients and those with other forms of non-cardiac liver disease. SS and SS/LS ratio may be a useful indicator of portal hemodynamics in Fontan patients.

RATIONALE & OBJECTIVE/OBJECTIVE:Patient education and decision support tools could facilitate decisions around the timing of antiviral therapy in patients living with both hepatitis C virus (HCV) infection and chronic kidney disease (CKD). We previously developed a tool through the HELP (Helping Empower Liver and Kidney Patients) study. This article evaluates the preliminary efficacy and usability of the tool among participants with both HCV infection and CKD. STUDY DESIGN/METHODS:Pre-post study pilot evaluation. SETTING & PARTICIPANTS/METHODS:Participants were at least 18 years old, were English speaking, and had a diagnosis of chronic HCV infection and CKD; they were seen in CKD clinics, dialysis units, and/or hepatology and liver transplantation clinics. INTERVENTION/METHODS:Electronic patient decision support tool. OUTCOMES/RESULTS:Participants' change in knowledge, certainty about choice, decision self-efficacy, patients' treatment preferences, and tool usability. RESULTS:0.48). LIMITATIONS/CONCLUSIONS:Single-site pilot study to explore preliminary tool efficacy and usability. CONCLUSIONS:This study suggests that a decision tool may support informed patient-centered choices among patients with HCV infection and CKD. Future studies should evaluate ways to improve care decisions in a larger sample using both paper-based and electronic materials. FUNDING/BACKGROUND:Merck & Co, Inc, Kenilworth, NJ. TRIAL REGISTRATION/BACKGROUND:Registered at clinicaltrials.gov with study number NCT03426787.

Hepatitis C direct acting antiviral (DAA) therapy has evolved so that infected patients with advanced chronic kidney disease (CKD) can now anticipate the opportunity for sustained virologic response equivalent to that of the broader population of patients with hepatitis C. This has revolutionized the field of transplantation as it relates to renal transplant candidates with hepatitis C and the use of grafts from hepatitis C virus (HCV) viremic donors. In treating this population of patients, special consideration must be given to the timing of anti-viral therapy and drug-drug interactions. Herein we review the pharmacokinetics of HCV DAA therapy in the setting of CKD and chronic renal replacement therapy. Highlighted are drug/drug interactions with special attention to therapies utilized in advanced CKD and immunosuppressants.

BACKGROUND & AIMS/OBJECTIVE:We aimed to evaluate the safety and effectiveness of 12 or 24 weeks treatment with ledipasvir and sofosbuvir, with or without ribavirin, in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis in routine clinical practice. Patients were followed in a multi-center, prospective, observational cohort study (HCV-TARGET). METHODS:We collected data from 667 treatment-experienced adults with chronic genotype 1 HCV infection who began treatment with ledipasvir and sofosbuvir, with or without ribavirin, from 2011 through September 15, 2016, according to the regional standards of care, at academic (n = 39) and community (n = 18) centers in the United States, Canada, Germany, and Israel. Information was collected from medical records and abstracted into a unique centralized data core. Independent monitors systematically reviewed data entries for completeness and accuracy. Demographic, clinical, adverse event, and virologic data were collected every 12 weeks during treatment and during the follow-up period. The primary efficacy endpoint was sustained virologic response, defined as a level of HCV RNA below the lower limit of quantification or undetectable at a minimum 64 days after the end of treatment (SVR12). The per-protocol population (n = 610) was restricted to patients who completed 12 or 24 weeks of treatment (±2 weeks) and had final virologic outcomes available. RESULTS:The per-protocol analysis revealed that 579 patients (93.8%) achieved an SVR12, including 50/51 patients who received ledipasvir and sofosbuvir for 12 weeks (98%), 384/408 patients who received ledipasvir and sofosbuvir for 24 weeks (94.1%), 68/70 patients who received ledipasvir and sofosbuvir with ribavirin for 12 weeks (97.1%), and 57/60 patients who received ledipasvir and sofosbuvir with ribavirin for 24 weeks (95%). On multivariate analysis, neither treatment duration nor the addition of ribavirin was associated with SVR12. Compensated cirrhosis (odds ratio [OR] compared to decompensated cirrhosis, 2.41; 95% CI, 1.16-5.02), albumin ≥ 3.5 g/dL (OR, 3.15; 95% CI 1.46-6.80), or total bilirubin ≤ 1.2 mg/dL (OR 3.34; 95% CI, 1.59-7.00) were associated with SVR12. CONCLUSIONS:In an analysis of safety and effectiveness data from the HCV-TARGET study, we found treatment with ledipasvir and sofosbuvir, with or without ribavirin, to be effective and well tolerated by treatment-experienced patients with genotype 1 HCV infection and compensated cirrhosis. There were no significant differences in rate of SVR12 among patients treated with ledipasvir and sofosbuvir for 12 or 24 weeks, with or without ribavirin. Patients with decompensated cirrhosis appear to benefit from the addition of ribavirin or extension of ledipasvir and sofosbuvir treatment to 24 weeks. ClinicalTrials.gov no: NCT10474811.