Faculty Bibliography

Purpose: There is a significant variation in the MELD scores and subsequent morbidity among liver recipients in the US. Larger OPOs consistently serve patients with advanced disease. Previous studies have shown 2.5 times greater prevalence of transplanted patients with MELD ³ 24 in these OPOs. CMS recent reimbursement adjustments may disproportionately affect certain programs given their increased prevalence of patients with more advanced disease. Methods: We analyzed the prevalence of transplants among patients with high UNET MELD scores and associated charges, costs, and reimbursements. We compared low, medium and high MELD score groups. Between 2014-2015, 43 liver transplants, all with >30 days survival, were analyzed. Results: Only 2 had MELD scores below 25 at transplant, both of which from live donors. 95% of patients had MELD scores above 25 and among these, 18% had MELD 40 or were Status 1. Compared to the national average, our MELD scores were: 25% 21-30 (National 21.5%, p >0.05), 70.5% 31-40 (National 25.9%, p < 0.001), and 4.5% Status 1 (National 5.9%, p >0.05). For MELD scores 21-30, hospital charges averaged $645,214 and reimbursements were $150,706. For MELD scores 31-39, charges were $686,720, and reimbursement were $139,776. Reviewing MELD 40/ Status 1 patients, the average hospital charges and reimbursements were $1,136,813 and $293,776 respectively. We compared their amounts to the MELD 40 patients who had hospital charges of $625,371 and reimbursements of $142,051 respectively. This demonstrated a loss of $843,037 for the first group and $483,320 for the second. Length of stay was 32 days for MELD 40/ Status 1 and 8 days for MELD 40 (p < 0.000). Conclusion: ³ 40 MELD patients have a huge financial impact on institutions. The difference between 25-39 and ³40 MELD points is greater than half a million dollars. These data reflect and include dialysis, intubation and ICU stay but do not include rehabilitation expenses which will be the focus of another study. We find that our institution, which likely reflects many institutions in our OPO, serves sicker patients and therefore incurs higher costs but receives lower reimbursements, as they are based on national expected care costs for healthier patients. A broader sharing in the US may equalize costs. Payers should take into account the added financial burden of performing transplant in high MELD patients

STUDY OBJECTIVE: In 2006, the Institute of Medicine emphasized substantial potential to expand organ donation opportunities through uncontrolled donation after circulatory determination of death (uDCDD). We pilot an out-of-hospital uDCDD kidney program for New York City in partnership with communities that it was intended to benefit. We evaluate protocol process and outcomes while identifying barriers to success and means for improvement. METHODS: We conducted a prospective, participatory action research study in Manhattan from December 2010 to May 2011. Daily from 4 to 12 pm, our organ preservation unit monitored emergency medical services (EMS) frequencies for cardiac arrests occurring in private locations. After EMS providers independently ordered termination of resuscitation, organ preservation unit staff determined clinical eligibility and donor status. Authorized parties, persons authorized to make organ donation decisions, were approached about in vivo preservation. The study population included organ preservation unit staff, authorized parties, passersby, and other New York City agency personnel. Organ preservation unit staff independently documented shift activities with daily operations notes and teleconference summaries that we analyzed with mixed qualitative and quantitative methods. RESULTS: The organ preservation unit entered 9 private locations; all the deceased lacked previous registration, although 4 met clinical screening eligibility. No kidneys were recovered. We collected 837 notes from 35 organ preservation unit staff. Despite frequently recounting protocol breaches, most responses from passersby including New York City agencies were favorable. No authorized parties were offended by preservation requests, yielding a Bayesian posterior median 98% (95% credible interval 76% to 100%). CONCLUSION: In summary, the New York City out-of-hospital uDCDD program was not feasible. There were frequent protocol breaches and confusion in determining clinical eligibility. In the small sample of authorized persons we encountered during the immediate grieving period, negative reactions were infrequent.

Learning Objectives: 1. Describe anatomic and physiologic aspects of creating left hepatic vein (LHV) to left portal vein (LPV) transjugular intrahepatic portosystemic shunts (TIPS). 2. Illustrate through a series of 15 cases the technical aspects unique to left-sided TIPS. 3. Understand outcomes of left-to-left TIPS creation for refractory ascites and variceal bleeding, compared with right and middle hepatic vein and right portal vein TIPS Background: TIPS creation is a primary treatment for complications of portal hypertension. Classically, the shunt is created between the right hepatic and right portal veins, owing to the relatively larger size of the right hepatic lobe that would theoretically increase safety and the potential for accessing one of multiple portal venous branches. LHV to LPV TIPS is much less frequently done, though preliminary studies have suggested possibly increased safety. In addition, there may be specific indications for left to left TIPS, most of which are anatomic in nature Clinical Findings/Procedure Details: Fifteen patients underwent successful LHV to LPV TIPS creation at a single institution from 11/2011 to 12/2014. Through a series of examples, the anatomy of left-to-left TIPS creation will be reviewed: left-sided TIPS tend to be shorter and less angulated compared with right-sided TIPS. Given the shorter trajectory, use of a pediatric needle for access may be considered. Patient outcomes regarding control of ascites and bleeding will be reviewed. Only 2 of 15 patients (13%) required a revision with angioplasty or further stent placement over 6 months. All of the patients were alive at 1 month post-TIPS. Conclusions: Left hepatic to left portal vein TIPS creation is safe and provides comparable outcomes compared with right-sided TIPS. Future controlled trials in centers frequently performing TIPS creation could clarify which approach is optimal. However, familiarity with the technical aspects of left-sided TIPS creation is essential as many patients have anatomy unfavorable for right-sided TIPS

Introduction: Velpatasvir (VEL) has demonstrated high SVR rates in patients with genotypes 1-6 HCV when used in combination with sofosbuvir (SOF). This Phase-3 study evaluated the safety and efficacy of the fixed-dose-combination (FDC) of SOF/VEL in HCV infected patients with decompensated liver disease. Methods: Genotype (GT) 1, 2, 3, 4 or 6 HCV infected patients with CPT-B cirrhosis were randomized 1:1:1 to receive SOF/VEL (400 mg/100 mg) daily for 12-weeks, SOF/VEL + weight-based RBV for 12-weeks, or SOF/VEL for 24-weeks. Patients with prior liver transplant or hepatocellular carcinoma were excluded. Results: Of the 267 patients treated, most were male (70 %), white (90 %) and treatment experienced (55 %). Patients had genotype 1 (78 %), 2 (4.5 %), 3 (15 %), 4 (3 %) or 6 (<1 %) HCV infection. The SVR12 rates are shown in Table 1. SOF/VEL + RBV for 12 weeks resulted in high SVR rates with virologic failure occurring in 1 (1 %) of GT-1 and 2 (15.2 %) of GT3 subjects respectively, including virologic breakthrough in a single GT3 patient. Among patients who achieved SVR, 47 and 56 % had improvements in CPT and MELD scores respectively. The most common adverse events were fatigue, headache, nausea). Overall 9 patients discontinued SOF/VEL due to adverse events. 47(18 %) patients experienced serious adverse events and there were 9 deaths; none were related to study drug. Conclusions: SOF/VEL + RBV for 12-weeks resulted in high SVR rates across all HCV genotypes in decompensated patients with early improvements in liver function. This regimen was well tolerated with AEs consistent with clinical sequelae of advanced liver disease and RBV. (Table Presented)

Purpose: Spontaneous bacterial peritonitis (SBP) is diagnosed by analysis of ascites obtained by image-guided paracentesis. We aimed to determine accurate predictors and whether SBP can occur in low-volume ascites. Material and methods: From 7/16 to 10/16, 243 paracenteses were performed in 99 patients (42 women, 57 men; mean age 63 years). Clinical symptoms, lab values, depth of the deepest pocket on ultrasound, total volume of ascites drained, cultures, neutrophil count (NC = total fluid nucleated cells x %neutrophils), and complications were recorded. Multiple logistic regressions were performed with age, gender, indication, cirrhosis, cancer, abdominal pain, fever, confusion, prior SBP, depth of largest fluid pocket documented on ultrasound, total volume of ascites drained, and most recent labs (INR, platelets, WBC, and sodium) as independent variables. Results: Of 243 cases, 11 cases were diagnosed with SBP by NC>250, 2 of which had positive cultures (Citrobacter and Enterococcus). One case with NC 123 had a positive culture with Citrobacter and considered SBP. Multiple logistic regression for diagnosis of SBP was significant (p<0.0001); abdominal pain (p=0.006) and depth of the deepest pocket (p=0.01) were the only significant independent predictors. All cases of SBP had deepest pockets >5cm; SBP cases had pockets of mean 7.7 cm, compared with 6.3 cm for negative cases (p=0.03). There were 2 major hemorrhagic complications (0.8%); regression demonstrated no predictors of complications. Conclusion: Large ascites pocket and abdominal pain predicted SBP; SBP was never diagnosed in patients with pockets <5cm. Given the potential for hemorrhagic complications (~1%), appropriate patient selection for paracentesis may include excluding patients with small ascites pockets on ultrasound

Background As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase. Methods We conducted a phase 3, open-label study involving both previously treated and previously untreated patients infected with HCV genotypes 1 through 6 who had decompensated cirrhosis (classified as Child-Pugh-Turcotte class B). Patients were randomly assigned in a 1:1:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks, sofosbuvir-velpatasvir plus ribavirin for 12 weeks, or sofosbuvir-velpatasvir for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. Results Of the 267 patients who received treatment, 78% had HCV genotype 1, 4% genotype 2, 15% genotype 3, 3% genotype 4, and less than 1% genotype 6; no patients had genotype 5. Overall rates of sustained virologic response were 83% (95% confidence interval [CI], 74 to 90) among patients who received 12 weeks of sofosbuvir-velpatasvir, 94% (95% CI, 87 to 98) among those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 86% (95% CI, 77 to 92) among those who received 24 weeks of sofosbuvir-velpatasvir. Post hoc analysis did not detect any significant differences in rates of sustained virologic response among the three study groups. Serious adverse events occurred in 19% of patients who received 12 weeks of sofosbuvir-velpatasvir, 16% of those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 18% of those who received 24 weeks of sofosbuvir-velpatasvir. The most common adverse events were fatigue (29%), nausea (23%), and headache (22%) in all patients and anemia (31%) in the patients receiving ribavirin. Conclusions Treatment with sofosbuvir-velpatasvir with or without ribavirin for 12 weeks and with sofosbuvir-velpatasvir for 24 weeks resulted in high rates of sustained virologic response in patients with HCV infection and decompensated cirrhosis. (Funded by Gilead Sciences; ASTRAL-4 ClinicalTrials.gov number, NCT02201901 .).

Introduction: HCV-infected patients with decompensated liver disease have significant morbidity and mortality with limited HCV treatment options. Velpatasvir (VEL, formerly GS-5816), is a pangenotypic HCV NS5A inhibitor that has demonstrated high SVR rates in patients with genotypes 1-6 HCV infection when used in combination with sofosbuvir (SOF). This Phase 3 study evaluated the safety and efficacy of the fixed dose combination (FDC) of SOF/VEL in HCV infected patients with decompensated liver disease. Methods: Genotype (GT) 1, 2, 3, 4 or 6 HCV infected patients with CPT-B cirrhosis were randomized 1:1:1 to receive SOF/VEL (400 mg /100 mg) daily for 12 weeks, SOF/VEL + weight based RBV for 12 weeks, or SOF/VEL for 24 weeks. Patients with prior liver transplant or hepatocellular carcinoma were excluded. Results: Of the 267 patients randomized and treated, the majority were treatment experienced (55 %), white (90%), males (70%), with IL28B non-CC (77%). Patients had genotype 1(78% overall, 60% 1a), 2 (4.5%), 3 (15%), 4 (3%) or 6 (<1%) HCV infection. The median CPT score was 8 (range 5-10) and median MELD score was (range 6-24). The SVR12 rates by GT are shown in table 1. SOF/VEL+RBV for 12 weeks resulted in high SVR rates with relapse occurring in 1 (1%) GT1 and 1 (8%) GT3 subjects respectively. A second GT3 patient in the SOF/VEL+RBV 12 Week group had on-treatment breakthrough with pharmacokinetic data consistent with nonadherence. There were no genotype 2, 4 and 6 virologic failures across all treatment arms. Among patients who achieved SVR, 47% and 56% had improvements in CPT and MELD scores by week 12 post EOT largely driven by increases in albumin and decreases in bilirubin. The most common adverse events were fatigue, headache, nausea and (anemia in the RBV containing arm with a median Hgb decrease of 1.4 g/dL). Overall 9 patients discontinued SOF/VEL due to adverse events. A total of 47 (18%) patients experienced serious adverse events (SAEs) with the most common being hepatic encephalopathy and sepsis; only 1 patient had SAEs assessed as related to SOF/VEL There were 9 deaths: sepsis (3); liver failure (2); cardiopulmonary arrest (2); myocardial infarction (1) and respiratory failure (1); none were assessed as related to study drug. Conclusions: In HCV infected patients with decompensated liver disease, SOF/ VEL+RBV for 12 weeks resulted in an overall SVR rate of 94.3% with high individual SVR rates across all HCV genotypes and resulted in early improvements in liver function. This regimen was well tolerated with AEs consistent with clinical sequelae of decompensated liver disease and RBV. (Table presented)