Efficacy of a two-dose hepatitis B vaccination with a novel immunostimulatory sequence adjuvant (Heplisav-B) on patients with chronic liver disease: a retrospective study.

Background: Patients with chronic liver disease (CLD) are more likely to have severe morbidity and mortality due to superimposed acute or chronic hepatitis B virus (HBV) infection and should receive routine vaccination against the virus. Heplisav-B is a two-dose, inactivated, yeast-derived vaccine that uses a novel immunostimulatory adjuvant. Our primary objective was to determine the efficacy of hepatitis B vaccination with Heplisav-B in patients with CLD. Methods: This retrospective cohort analysis included patients ≥18 years old with CLD who received Heplisav-B from January 2018 to January 2021. All patients had anti-HBs <10 IU/L prior to vaccination and received two doses of Heplisav-B. Post-vaccination anti-HBs of ≥10 IU/L was considered successful vaccination. Basic demographic information, laboratory markers, and medical history were collected from the electronic health record. Results: A total of 120 patients were included in analysis. The average age of patients was 59 years, 37% were female, and the most common etiology of liver disease was nonalcoholic fatty liver disease. Median days from 2nd vaccination to post-vaccination HBsAb levels was 121 days. 81/120 (67.5%) of patients had evidence of active immunity after receipt of Heplisav-B. On multivariable analysis, age >50 was associated with reduced odds of successful vaccination (OR =0.19, 95% CI: 0.03-0.76). Conclusions: In patients with CLD, Heplisav-B's overall efficacy (67.5%) is greater than reports of Engerix-B (33-45%), and thus is an effective hepatitis B vaccine in this patient population, particularly in cirrhotic patients. Further studies regarding this vaccine are needed in patients with CLD and after liver transplantation.

Does Donor Allograft Microsteatosis Matter? Comparison of Outcomes in Liver Transplantation With a Propensity-Matched Cohort.

It has been suggested that microsteatosis does not negatively impact graft survival following liver transplantation (LT). The present study represents the largest series on donor livers with significant microsteatosis and investigates the impact of microsteatosis on perioperative factors such as postreperfusion syndrome (PRS), early allograft dysfunction (EAD), and postoperative renal dysfunction. Clinical outcomes of all patients undergoing LT with donor livers with isolated microsteatosis (≥30%; n = 239) between 2000 and 2017 were compared with a propensity score-matched cohort of patients undergoing LT with donor livers with no steatosis (n = 239). Patients in the microsteatosis group had a higher rate of PRS (33.1% versus 24.2%; P = 0.03), EAD (38.2% versus 23.0%; P < 0.001), and continuous renal replacement therapy (CRRT) requirement following LT (10.9% versus 3.6%; P = 0.002) than the no steatosis group. No difference in patient (P = 0.33) or graft survival (P = 0.18) was observed between the 2 groups. On multivariate regression, livers with microsteatosis had an increased risk of graft loss with retransplant recipients (hazard ratio [HR], 1.59; P < 0.001), increasing Model for End-Stage Liver Disease (MELD) score (HR, 1.13; P = 0.01), and organs from donation after circulatory death donors (HR, 1.46; P = 0.003). In conclusion, recipients of donor livers with significant microsteatosis are at an increased risk of PRS, EAD, and postoperative renal dysfunction requiring CRRT. Livers with significant microsteatosis should be avoided in retransplant recipients and in recipients with high biological MELD scores. Once appropriately selected recipients of these livers are able to overcome the initial perioperative implications of using these donor livers, longterm patient and graft survival is similar to recipients receiving grafts with no steatosis.

The Emerging Role of Nurse Practitioners and Physician Assistants in Liver Transplantation.

The evolving role of nurse practitioners (NPs) and physician assistants (PAs) in the United States continues to progress. NP and PA responsibilities have expanded from primary care practices to medical and surgical specialties. They provide acute care in hospitals and intensive care units, and they serve as educators, lobbyists, and researchers. Questions have arisen from NP/PA leaders, physician leaders, and administrators on how to best implement a successful NP/PA model within their practice. This article reviews some common themes in the literature by looking at the current state of NP/PA practice, outlines some practice models established therein, and provides recommendations for implementing a successful NP/PA model in a liver transplant practice.

Intra-operative predictors of postoperative Takotsubo syndrome in liver transplant recipients-An exploratory case-control study.

INTRODUCTION: Takotsubo syndrome (TTS), also known as Takotsubo cardiomyopathy or stress-induced cardiomyopathy, has been described following a variety of surgeries and disease states. The relationship between intra-operative anesthesia management and the development of this syndrome has never been fully elucidated. OBJECTIVES: The primary objective of this study was to determine the relationship of multiple intra-operative factors on the pathogenesis of TTS. METHODS: A single-center retrospective review of all liver transplants performed at Mayo Clinic Florida from January 2005 to December 2014. Patients developing left ventricular dilation and a concomitant decrease in ejection fraction, a negative cardiac catheterization, or stress test within 30 days of transplantation were identified. Cases were matched 2:1 to controls with respect to MELD, age, sex, and indication for transplantation. Our evaluation included liver graft characteristics, intra-operative medications, and intra-operative hemodynamic measurements. RESULTS: We identified 24 cases of TTS from a pool of 1752 transplants, for an incidence of 1.4%. No statistically significant differences in intra-operative measures between the two groups were identified (all P ≥ .08). CONCLUSION: Our exploratory, single-center retrospective review evaluating 46 intra-operative characteristics found no association with the development of TTS.

Liver Transplantation for Hepatocellular Carcinoma: Impact of Wait Time at a Single Center

ABSTRACT Introduction and aim. Liver transplantation (LT) provides durable survival for hepatocellular carcinoma (HCC). However, there is continuing debate concerning the impact of wait time and acceptable tumor burden on outcomes after LT. We sought to review outcomes of LT for HCC at a single, large U.S. center, examining the influence of wait time on post-LT outcomes. Material and methods. We reviewed LT for HCC at Mayo Clinic in Florida from 1/1/2003 until 6/30/2014. Follow up was updated through 8/1/ 2015. Results. From 2003-2014,978 patients were referred for management of HCC. 376 patients were transplanted for presumed HCC within Milan criteria, and the results of these 376 cases were analyzed. The median diagnosis to LT time was 183 days (8 - 4,337), and median transplant list wait time was 62 days (0 -1815). There was no statistical difference in recurrence-free or overall survival for those with wait time of less than or greater than 180 days from diagnosis of HCC to LT. The most important predictor of long term survival after LT was HCC recurrence (HR: 18.61, p < 0.001). Recurrences of HCC as well as survival were predicted by factors related to tumor biology, including histopathological grade, vascular invasion, and pre-LT serum alpha-fetoprotein levels. Disease recurrence occurred in 13%. The overall 5-year patient survival was 65.8%, while the probability of 5-year recurrence-free survival was 62.2%. Conclusions. In this large, single-center experience with long-term data, factors of tumor biology, but not a longer wait time, were associated with recurrence-free and overall survival.

Liver Transplantation for Hepatocellular Carcinoma: Impact of Wait Time at a Single Center.

INTRODUCTION AND AIM: Liver transplantation (LT) provides durable survival for hepatocellular carcinoma (HCC). However, there is continuing debate concerning the impact of wait time and acceptable tumor burden on outcomes after LT. We sought to review outcomes of LT for HCC at a single, large U.S. center, examining the influence of wait time on post-LT outcomes. MATERIAL AND METHODS: We reviewed LT for HCC at Mayo Clinic in Florida from 1/1/2003 until 6/30/2014. Follow up was updated through 8/1/ 2015. RESULTS: From 2003-2014, 978 patients were referred for management of HCC. 376 patients were transplanted for presumed HCC within Milan criteria, and the results of these 376 cases were analyzed. The median diagnosis to LT time was 183 days (8 - 4,337), and median transplant list wait time was 62 days (0 - 1815). There was no statistical difference in recurrence-free or overall survival for those with wait time of less than or greater than 180 days from diagnosis of HCC to LT. The most important predictor of long term survival after LT was HCC recurrence (HR: 18.61, p < 0.001). Recurrences of HCC as well as survival were predicted by factors related to tumor biology, including histopathological grade, vascular invasion, and pre-LT serum alpha-fetoprotein levels. Disease recurrence occurred in 13%. The overall 5-year patient survival was 65.8%, while the probability of 5-year recurrence-free survival was 62.2%. CONCLUSIONS: In this large, single-center experience with long-term data, factors of tumor biology, but not a longer wait time, were associated with recurrence-free and overall survival.

Predictors and impacts of hospital readmissions following liver transplantation.

While liver transplantation is the definitive therapy for end stage liver disease, it remains a major procedure, with many potential complications. Hospital readmissions after the initial hospitalization for liver transplantation can be associated with adverse outcomes, increased cost, and resource utilization. Our aim was to define the incidence and reasons for hospital readmission after liver transplant and the impact of readmissions on patient outcomes. We retrospectively analyzed 30- and 90-day readmission rates and indications in patients who underwent liver transplant at a large-volume transplant center over a 3-year period. Four hundred seventy-nine adult patients underwent their first liver transplant during the study period. The 30-day readmission rate was 29.6%. Recipient and donor age, etiology of liver disease, biological Model for End-Stage Liver Disease score, and cold ischemia time were similar between patients who were readmitted within 30 days and those who were not readmitted. Readmissions occurred in 25% of patients who were hospitalized prior to liver transplant compared to 30% who were admitted for liver transplant. The most common indications for readmission were infection, severe abdominal pain, and biliary complications. Early discharge from hospital (fewer than 7 days after liver transplant), was not associated with readmission; however, a prolonged hospital stay after liver transplant was associated with an increased risk of readmission (p = 0.04). In conclusion, patients who undergo liver transplant have a high rate of readmission. In our cohort, readmissions were unrelated to pre-existing recipient or donor factors, but were associated with a longer hospital stay after liver transplant.

Preexisting atrial fibrillation and cardiac complications after liver transplantation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and it is associated with increased cardiovascular morbidity and all-cause mortality. Our aim was to determine the impact of preexisting AF on patients undergoing liver transplantation (LT). A retrospective case-control study was performed. Records from patients who underwent LT between January 2005 and December 2008 at Mayo Clinic Florida were reviewed. Patients with preexisting AF were identified and matched to patients who did not have a diagnosis of AF. Thirty-two of 717 LT recipients (4.5%) had AF before LT. These patients were compared to a control group of 63 LT recipients. Pre-LT left ventricular hypertrophy (P = 0.03), a history of congestive heart failure (P = 0.04), and a history of stroke or transient ischemic attack (P = 0.03) were significantly more prevalent in patients with AF versus controls. Intraoperative adverse cardiac events (P = 0.02) and AF-related adverse postoperative events (P < 0.001) were more common in the recipients with known AF. Six patients with paroxysmal AF (19%) developed chronic/persistent AF postoperatively. Graft survival and patient survival were similar in the groups. Although patients with AF had a higher incidence of intraoperative cardiac events, a higher cardiovascular morbidity rate, and a complicated postoperative course, this did not affect overall graft and patient survival.

Reversible non-ischaemic cardiomyopathy and left ventricular dysfunction after liver transplantation: a single-centre experience.

BACKGROUND & AIMS: Non-ischaemic cardiomyopathy (NIC) is an early complication of liver transplantation (LT). Our aims were to define the prevalence, associated clinical factors, and prognosis of this condition. METHODS: A retrospective study was performed on patients undergoing LT at our institution from January 2005 to December 2012. Patients who developed NIC were identified. Data collected included demographic and clinical data. RESULTS: A total 1460 transplants were performed in this period and seventeen patients developed NIC. Pretransplant median QTc interval was 459 (range, 405-530), and median E/A ratio was 1 (range, 0.71-1.67). Fourteen patients (82%) were severely malnourished and required nutritional support. Thirteen patients (76%) had renal insufficiency. Median time to onset was 2 days post-transplant (range, 0-20). Echocardiograms showed global left ventricular hypokinesis and a decrease in ejection fraction (EF) from a median of 65% (range, 50-81) pretransplant to a median of 21% (range, 15-32). Median raw model for end-stage liver disease (MELD) score was 29 in patients with NIC vs. 18 in patients without cardiomyopathy (P = 0.01). There was no significant difference between recipients with NIC vs. recipients without cardiomyopathy regarding donor age, donor risk index, and cold and warm ischaemia time. Recovery of cardiac function occurred in 16 patients, with a median EF of 44% (range, 25-65%) at the time of discharge. The last echocardiogram available showed a median EF of 59% (range, 49-73%). One-year survival of NIC patients was 94.1%. CONCLUSION: Non-ischaemic cardiomyopathy is a rare complication after LT. Patients with NIC are critically ill, with high MELD score, and severe malnutrition.

Multicenter experience using telaprevir or boceprevir with peginterferon and ribavirin to treat hepatitis C genotype 1 after liver transplantation.

The safety, efficacy, and effect on immunosuppression levels of telaprevir (TVR) or boceprevir (BOC) in combination with peginterferon (PEG-IFN) and ribavirin (RBV) in recipients of liver transplantation (LT) with hepatitis C virus (HCV) genotype 1 have not been defined. We report our 3 centers' preliminary experiences with administering triple antiviral treatment protocols containing PEG-IFN, RBV, and TVR or BOC. Patients with biopsy-proven HCV recurrence (METAVIR grade ≥ 3 and/or stage ≥ 2) received TVR with PEG-IFN/RBV for 12 weeks and then PEG-IFN/RBV for 36 weeks or BOC with PEG-IFN/RBV for 44 weeks after 4 weeks of lead-in PEG-IFN/RBV. Maintenance immunosuppression was changed to cyclosporine whenever possible, and the levels were followed closely. PEG-IFN/RBV dose adjustments were based on patients' tolerance. Sixty patients started triple antiviral treatment, and they were followed for up to 66 weeks (mean = 35 weeks); all were followed at least 12 weeks. Thirty of the 35 patients treated with TVR (86%) achieved undetectable HCV RNA levels after an average of 6 weeks, whereas 12 patients (48%) in the BOC-treated group achieved undetectable HCV RNA levels after a mean of 11 weeks. According to an intention-to-treat analysis, 14 of 21 TVR-treated patients (67%) and 10 of 22 patients who received BOC (45%) achieved undetectable HCV RNA levels at week 24 without viral breakthrough at the last follow-up. Cytopenias complicated both regimens; all patients required dose reductions of PEG-IFN and/or RBV or the administration of hematological growth factors. One death occurred in each group on triple antiviral treatment. In conclusion, TVR or BOC combined with PEG-IFN/RBV achieved on-treatment virological response rates of approximately 50% to 60% in patients with recurrent HCV after LT, but significant side effects were common.

Long term survival and complications after liver transplantation in patients with chronic hepatitis B.

BACKGROUND: Following introduction of effective antiviral prophylaxis, recurrent hepatitis B after liver transplantation (LT) has become a rare event. MATERIAL/METHODS: From 1998 to 2001, 402 patients underwent 467 LTs at our center including 24 individuals (28 LTs) with chronic hepatitis B. All patients received HBIg prophylaxis; 23 in combination with lamivudine and one (YMDD mutant) received adefovir. RESULTS: Eleven patients (46%) had HCC (five outside the Milan criteria); only one died from tumor recurrence four years post LT. The one-year graft and patient survival were 87% and 92%, respectively. Currently 19 patients (79%) are alive with well functioning grafts (minimum follow up of >7 years). No patient developed recurrent hepatitis B; 12 currently receive lamivudine/HBIg, 3 lamivudine monotherapy, 3 discontinued antivirals. Follow up liver biopsies showed minimally active or no active hepatitis and negative HBV immunostains in all patients. Long term comorbid conditions included hypertension (77%), chronic renal failure (50%), diabetes mellitus (77%), hyperlipidemia (36%), obesity (55%), malignancies (37%) and neuropsychiatric disorders (55%). During the study period, 24 individuals (6%) were transplanted for chronic hepatitis B as opposed to only 38 individuals (3.3%) from 2002 to 6/2008 (1298 LTs in 1162 patients). CONCLUSIONS: LT for chronic HBV produced excellent long term results despite inclusion of patients with HCC outside the Milan criteria. Long term medical complications must be considered. Indication for LT for chronic HBV is declining but long term development of resistance remains a matter of concern.

Dual hepatitis virus infections in liver transplant: case report and a review of the literature.

BACKGROUND: Liver transplantation (LT) using grafts from anti-HBVcore antibody-positive (anti-HBVcAB+) donors carry risk for development of hepatitis B virus (HBV) infection. The long-term course of hepatitis C virus (HCV) patients receiving anti-HBVcAB+ grafts is poorly understood. PATIENTS AND METHODS: A patient with chronic hepatitis C received an anti-HBVc+ graft and developed de novo hepatitis B after four months. We describe the 14 HCV patients who received antiHBVc+ grafts and the condition of disease. RESULTS: Hepatitis B was treated successfully with lamivudine. One year later, breakthrough infection developed with a lamivudine-resistant mutant. Addition of adefovir led to HBV surface antigen to surface antibody seroconversion after two yr, which was maintained long term. Antiviral therapy was discontinued. Liver biopsy revealed minimal histologic changes up to eight yr post-LT. Survival of 14 recipients of antiHBVc+ allografts and 180 recipients of antiHBVc-negative grafts was equal (minimum follow up of five yr). Liver biopsies at four yr showed grade 0/1 and stage 0/1 in >70%; only two patients showed bridging fibrosis. A literature review of dual hepatitis virus infection revealed an overall milder course of hepatitis post-LT. CONCLUSION: The outcome of HCV patients receiving anti-HBc+ grafts is good and may be associated with a milder course of recurrent HCV.

Liver retransplantation of patients with hepatitis C infection is associated with acceptable patient and graft survival.

Infection with hepatitis C virus (HCV) is the leading cause of liver transplantation (LT), while liver retransplantation (RT) for HCV is controversial as a result of concerns over poor outcomes. We sought to compare patient and graft survival after RT in patients with and without HCV. We performed a retrospective chart review of all patients undergoing RT at our center between February 1998 and April 2004. Indications for RT, HCV status, patient, and donor characteristics, laboratory values, and hospitalization status at RT were collected. A total of 108 patients (48 HCV and 60 non-HCV) underwent RT during the study period, with mean post-RT follow-up of 1,096 days (range, 0-2,888 days). Grafts from donors aged>60 years were used less frequently in HCV patients at RT (6%) compared with LT (47%), P<0.001. There was no difference between HCV vs. non-HCV patients in 1- and 3-year patient survival (respectively, 79% vs. 63%, and 71% vs. 63%) and graft survival (respectively, 67% vs. 66%, and 59% vs. 56%). Post-RT mortality and graft failure in HCV patients occurred within the first year in 89% of patients, and 83% were unrelated to HCV recurrence. We conclude that patients should not be excluded from consideration for retransplantation solely on the basis of a diagnosis of HCV.