Addressing the Burden and Management Strategies for Disparities and Inequities Among Liver Transplant Professionals: The ILTS Experience.

Medical professional environments are becoming increasingly multicultural, international, and diverse in terms of its specialists. Many transplant professionals face challenges related to gender, sexual orientation or racial background in their work environment or experience inequities involving access to leadership positions, professional promotion, and compensation. These circumstances not infrequently become a major source of work-related stress and burnout for these disadvantaged, under-represented transplant professionals. In this review, we aim to 1) discuss the current perceptions regarding disparities among liver transplant providers 2) outline the burden and impact of disparities and inequities in the liver transplant workforce 3) propose potential solutions and role of professional societies to mitigate inequities and maximize inclusion within the transplant community.

Weight Loss and Weight Regain in Usual Clinical Practice: Results From the TARGET-NASH Observational Cohort.

First-line treatment for nonalcoholic fatty liver disease (NAFLD) focuses on weight loss through lifestyle modifications.1,2 Weight loss ≥5% results in reduction of steatosis and weight loss ≥10% has been associated with improvement in hepatic inflammation and fibrosis.3 The incidence and sustainability of weight loss among patients with NAFLD were estimated and associating factors identified.

Preliver transplant red cell distribution width predicts postliver transplant mortality.

PURPOSE: Prognostication following liver transplantation is limited. Red cell distribution width (RDW) has been associated with morbidity and mortality in a variety of diseases. We hypothesize RDW is predictive of mortality postliver transplantation. METHODS: We performed a retrospective cohort study of all consecutive liver transplantation recipients at a tertiary care center from January 1, 2012 to December 31, 2012. The primary end point was association of RDW with one-year mortality. Statistical analysis was performed using the Mann-Whitney test, independent samples t test, and regression analysis. Discrimination was assessed by calculating area under receiver operating curves (AUC). A P-value <.05 was considered significant. RESULTS: RDW was positively associated with one-year mortality (P<.001). The mean difference for survivors compared to nonsurvivors was 3.9% (95% CI 1.9%-5.9%). The AUC for RDW was 0.831 (95% CI 0.727-0.935), compared to 0.723 (0.539-0.908) for total bilirubin and 0.704 (0.479-0.929) for the international normalized ratio. CONCLUSIONS: To our knowledge, this is the first report of an association of RDW with post-LT mortality and the results show the predictive value of pre-LT RDW for one-year mortality.

Lack of Clostridium difficile infection in patients treated with rifaximin for hepatic encephalopathy: a retrospective analysis.

GOALS: The purpose of this study was to assess the incidence of Clostridium difficile infection in patients who received rifaximin for the treatment of hepatic encephalopathy (HE). METHODS: Medical charts of patients who received rifaximin for the treatment of HE were reviewed. The number of patients who developed diarrhea during treatment with rifaximin and results of latex agglutination assays to detect C. difficile in stool samples were analyzed. RESULTS: A total of 211 patients received rifaximin for HE. Of these, 152 were treated in a university practice and 59 were treated in community practices. The mean dose of rifaximin was 1055 mg/d (range, 600 to 1600 mg/d) for a mean duration of 250 days (range, 180 to 385 d). Eighteen patients developed diarrhea during rifaximin treatment. None of these patients tested positive for C. difficile. CONCLUSIONS: This study demonstrates that treatment of HE with the safe, nonsystemic, gut-selective antibiotic rifaximin was not associated with the development of C. difficile infection.

Obesity portends increased morbidity and earlier recurrence following liver transplantation for hepatocellular carcinoma.

BACKGROUND: Obesity has been associated with poor oncologic outcomes following pancreatoduodenectomy for pancreatic cancer. However, there is a paucity of evidence on the impact of obesity on postoperative complications, oncologic outcome and survival in patients with hepatocellular carcinoma (HCC) undergoing orthotopic liver transplantation (OLT). METHODS: From a database of over 1000 patients who underwent OLT during 1996-2008, 159 patients with a diagnosis of HCC were identified. Demographic data, body mass index (BMI), perioperative parameters, recurrence and survival were obtained. Complications were grouped according to Clavien-Dindo grading (Grades I-V). RESULTS: There were increased incidences of life-threatening complications in overweight (58%) and obese (70%) patients compared with the non-obese patient group (41%) (P < 0.05). Furthermore, the incidence of recurrence of HCC was doubled in the presence of overweight (15%) and obesity (15%) compared with non-obesity (7%) (P < 0.05). Time to recurrence also decreased significantly. Differences in mean ± standard deviation survival in the overweight (45 ± 3 months) and obese (41 ± 4 months) groups compared with the non-obese group (58 ± 6 months) did not reach statistical significance. CONCLUSIONS: These findings indicate that BMI is an important surrogate marker for obesity and portends an increased risk for complications and a poorer oncologic outcome following OLT for HCC.

Durability of rifaximin response in hepatic encephalopathy.

GOALS: To evaluate the durability of the response to rifaximin for treatment of hepatic encephalopathy (HE). BACKGROUND: The nonsystemic antibiotic rifaximin has been approved for maintenance of HE remission, and several studies have indicated the efficacy of rifaximin for acute HE; however, the duration of therapeutic response for >6 months remains unknown. STUDY: Medical records of patients with cirrhosis who received rifaximin maintenance therapy for HE between January 2004 and May 2009 were reviewed. Model for end-stage liver disease (MELD) scores were obtained every 3 months during therapy. RESULTS: Of 203 patients with HE (Conn score ≥2), 149 received rifaximin monotherapy (400 to 1600 mg/d) and 54 received rifaximin (600 to 1200 mg/d) and lactulose (90 mL/d) dual therapy. Maintenance of HE remission for 1 year occurred in 81% and 67% of patients who received rifaximin monotherapy and rifaximin and lactulose dual therapy, respectively. Patient populations with a baseline mean MELD score ≤20 had few overt HE events, suggesting increased response to rifaximin in these patients. CONCLUSIONS: Rifaximin is effective for the management of HE in patients with cirrhosis, particularly in populations with MELD scores ≤20. Additional studies are needed to investigate the potential association between MELD scores and the efficacy of HE treatments.

Liver transplantation trends in the HIV population.

There is a paucity of information on the utilization patterns of liver transplantation (LT) for HIV-positive individuals. The aim of this study is to examine the trends in LT of HIV patients in the US. This study was a retrospective analysis using the UNOS database (1999-2008). There were 135 HIV-positive patients. There was a steady increase in the number of LT recipients over time as well as regional variation. Ethnic minorities accounted for 33.3% and there was no ethnic difference in survival. Though LT for HIV-positive patients is on the rise, significant variations exist in patient demographics, geographic location, and insurance payer.

The Association Between Alcoholic Liver Disease and Alcohol Tax.

BACKGROUND: The incidence of alcoholic liver disease (ALD) has increased, causing it to become a primary indication for liver transplantation in the United States. We hypothesized an association between alcohol taxation and prevalence of ALD. METHODS: We conducted a retrospective study of united network for organ sharing (UNOS) waitlist additions for liver transplantation between January 2007 and December 2016. We also analyzed the average excise tax (2007-2016) for beer, wine, and spirits in listing states of liver transplant waitlist additions (LTWA). RESULTS: There were 104 805 adult UNOS LTWA with assigned diagnoses, an annual increase from 22% to 28%. There were 24 316 LTWA with ALD diagnosis. The mean value for beer tax was significantly lower for ALD patients than for non-ALD patients across all age groups (P < .001). The analysis demonstrated significantly more ALD in waitlisted patients 35-54 years of age (30%), compared with 18-34 years (10%) and ≥55 years (20%), P < .001. The data confirmed significantly more ALD Medicaid patients in the 35-54 year age group (28%) compared with other age groups, P < .001. DISCUSSION: Our research demonstrated an association between lower beer tax and higher ALD prevalence across all age groups. We found a larger percentage of middle-aged (35-54 years) Medicaid patients listed with ALD. These findings raise the need for further investigation of a potential public health concern for an association between ALD and beer tax, especially for middle-aged patients of lower socioeconomic status.

Rifaximin for the treatment of recurrent Clostridium difficile infection after liver transplantation: A case series.

Previous data have suggested that the nonsystemic antibiotic rifaximin may be effective for the treatment of Clostridium difficile infection (CDI). This single-center retrospective study evaluated the efficacy of rifaximin for the treatment of CDI refractory to standard treatments in patients who had received liver transplants. Among 205 patients who had received liver transplants between July 2001 and December 2007, 3 patients with a confirmed diagnosis of C. difficile experienced recurrent diarrhea even though they received standard therapy. Patient 1, a 56-year-old male, patient 2, a 62-year-old male, and patient 3, a 73-year-old female, developed CDIs 190, 318, and 2310 days after transplantation, respectively. All patients experienced symptom recurrences after oral metronidazole therapy (250 mg 3 times daily for either 14 or 28 days) and after oral vancomycin therapy (125 mg 4 times daily for 14 days). Long-term vancomycin treatment (ie, 28 days) was required for patients 1 and 2. Vancomycin was discontinued in patient 3 because of increased creatinine levels. Oral rifaximin (400 mg 3 times daily) was initiated immediately after discontinuation of vancomycin therapy. Within 36 to 48 hours of the initiation of rifaximin treatment, diarrheal symptoms were resolved in all patients. After completing a 28-day course of rifaximin, patient 1 remained symptom-free during 185 days of follow-up, and patient 2 remained symptom-free during 250 days of follow-up. Patient 3 reported no symptoms within 155 days after the completion of rifaximin treatment. These findings suggest that rifaximin may be effective for the treatment of recurrent CDI and may provide a therapeutic option for CDI in immunocompromised patients.

Liver transplantation in the ethnic minority population: challenges and prospects.

In the USA, end-stage liver disease (ESLD) is a major cause of morbidity and mortality among ethnic minorities. Ethnic populations vary with respect to chronic liver disease prevalence, access to transplantation, and therapeutic outcomes post liver transplantation. These ethnic differences present unique challenges to healthcare professionals involved in the care of patients with chronic liver disease prior and post transplantation. This review will discuss the variations and challenges of liver transplantation in the ethnic minority population.

Hepatitis C and Racial Disparity in Liver Transplant Waitlist Additions : Separate Not Equal.

BACKGROUND: In 2014, direct-acting antivirals (DAAs) became available for hepatitis C virus (HCV) with successful results. Since their implementation, the rate of HCV waitlist (WL) for liver transplantation (LT) has decreased, but significant ethnic disparities exist. We hypothesized that the rate of decline for HCV WL for LT is different across the various racial groups. METHODS: We conducted a retrospective cohort study using Organ Procurement and Transplantation Network data reports of adult LT candidates from 2014 to 2018. RESULTS: Overall, there was a decline in HCV WL rates for all ethnic groups (Caucasians, African Americans [AA], and Hispanics). However, the WL rates were significantly higher in AA compared with Caucasians each year, and this trend was continuous across the 5-year period. There were no differences in WL rates between Caucasians and Hispanics. DISCUSSION: The results show that health care disparities related to HCV disproportionately affect AA. The factors associated with this disparity need to be explored further to develop mechanisms to address these differences. By understanding the HCV treatment disparities across racial groups, modifications to HCV treatment nationwide can be adopted. Additional emphasis should be placed on AA to help reduce their WL rate, as well as redistributing resources to promote health care equity.

Cost Utilization and the Use of Pulmonary Function Tests in Preoperative Liver Transplant Patients.

BACKGROUND: Pulmonary function tests (PFTs) are currently recommended for liver transplant candidates. We hypothesized that PFTs may not provide added clinical value to the evaluation of liver transplant patients. METHODS: We conducted a retrospective cohort study of adult cadaveric liver transplants from 2012 to 2018. Abnormal PFTs were defined as restrictive disease of diffusing capacity of the lungs for carbon monoxide (DLCO) <80% or obstructive disease of ratio of forced expiratory volume in the first 1 second to the first vital capacity of the lungs (FEV1/FVC) <70%. RESULTS: We analyzed data on 415 liver transplant patients (358 abnormal PFT results and 57 normal results). The liver transplant patients with abnormal PFTs had no difference in number of intensive care unit (ICU) days (P = .68), length of stay (P = .24), or intubation days (P = .33). There were no differences in pulmonary complications including pleural effusion (P = .30), hemo/pneumothorax (P = .74), pneumonia (P = .66), acute respiratory distress syndrome (P = .57), or pulmonary edema (P = .73). The significant finding between groups was a higher rate of reintubation in liver transplant patients with normal PFTs (P = .02). There was no difference in graft survival (P = .53) or patient survival (P = .42). DISCUSSION: Abnormal PFTs, found in 86% of liver transplant patients, did not correlate with complications, graft failure, or mortality. PFTs contribute to the high cost of liver transplants but do not help predict which patients are at risk of postoperative complications.

Pre-Liver Transplant Coronary Artery Disease Workup for Low-Risk Patients.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of mortality following orthotopic liver transplant, yet there is no standardized protocol for pre-liver-transplant coronary artery disease assessment. The main objective of this study was to determine the agreement between 2 methods of cardiac risk assessment: dobutamine stress echocardiogram (DSE) and coronary calcium score (CCS) and to determine which test was best able to predict coronary calcification in low-risk patients. METHODS: A retrospective study was performed using the medical records of 436 patients who received cardiac clearance for a liver transplant. A total of 152 patients' medical records were included based on the inclusion of patients who had received both DSE and CCS. A kappa coefficient was calculated to determine the agreement between the DSE and CCS results. In addition, the positive predictive values (PPVs) of both the CCS and DSE along with cardiac catheterization indicating abdominal occlusion were analyzed to compare the accuracy of the 2 tests. RESULTS: It was determined that there was a 12% agreement between DSE results and CCS. It was found that the DSE had a PPV of 56% and the CCS had a PPV of 80%. CONCLUSION: From this data, it was concluded that there was no agreement between the results of the CCS and the DSE. While neither the CCS nor the DSE presents an optimal method of risk assessment, the CCS had a much higher PPV and was therefore determined to be the more accurate test.

Access to liver transplantation in the MELD era: role of ethnicity and insurance.

Factors contributing to inequitable access to liver transplantation include socioeconomic status, geographic location, and delayed referral. The aim of this study is to identify the factors associated with a high MELD at the time of listing. Using the UNOS database, we identified all adults listed from 2002 to 2006. Data collected included demographics, insurance payor (private and government, i.e., Medicaid and non-Medicaid), diagnosis, and MELD score categorized as low (<20) and high (>or=20). The results obtained show that a high MELD was associated with age, ethnicity, and insurance (P < 0.001). By multivariate analysis, insurance (OR = 1.21, 95% CI = 1.13-1.30, P < 0.001) and ethnicity (OR = 1.55, 95% CI = 1.28-1.88, P < 0.001) were independently associated with high MELD. In conclusion, ethnic minorities and liver transplant candidates with Medicaid are more likely to have a high MELD score at initial listing. The above results suggest that the type of insurance and ethnicity are independently associated with a high MELD (i.e., sicker patients).

Malleable Transplant Criteria: At What Cost?

An 18-year-old male who had been diagnosed at age 7 with a rare, progressive liver disease was referred to the transplant center and received a transplant, even though he did not meet the center's criteria for a patient with hepatopulmonary syndrome (HPS). Complications required relisting the patient urgently, but he eventually fully recovered; total hospital charges for his treatment exceeded $5 million. Reflection upon the case resulted in analysis of two ethical questions: primarily, clinician obligation to balance the provision of actuarially fair health care to society against the healing of a single patient; secondarily, the effects of malleable transplant criteria on trust in the patient selection process. We affirmed that physicians should not be principally responsible for justifying financial investment to society or for upholding beneficence beyond the individual physician and patient relationship in order to contain costs. We concluded, however, that such instances, when combined with manipulation of transplant center criteria, pose a potential threat to public trust. We therefore suggested that transplant centers maintain independent ethics committees to review such cases.

Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir in Patients With Hepatitis C Virus Genotype 1 or 4 Infection and Advanced Kidney Disease.

INTRODUCTION: Hepatitis C virus (HCV) infection is common in patients with end-stage renal disease. We investigated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) ± dasabuvir (DSV) ± ribavirin (RBV) in 2 phase 3, open-label, multicenter studies in patients with stage 4 or 5 chronic kidney disease (CKD). METHODS: RUBY-I, Cohort 2 enrolled treatment-naïve or -experienced patients with HCV genotype (GT) 1a or 1b infection, with or without cirrhosis. Patients received 12 weeks (24 weeks for GT1a patients with cirrhosis) of OBV/PTV/r + DSV; all GT1a patients received RBV. RUBY-II enrolled treatment-naïve patients with GT1a or GT4 infection without cirrhosis. All patients received 12 weeks of RBV-free treatment: OBV/PTV/r + DSV for GT1a-infected patients; OBV/PTV/r for GT4-infected patients. The primary endpoint was sustained virologic response at posttreatment week 12 (SVR12). RESULTS: RUBY-I, Cohort 2 and RUBY-II enrolled 66 patients, including 50 (76%) on dialysis; 15 (23%) had compensated cirrhosis. Overall, the SVR12 rate was 95% (63/66); 1 patient had virologic failure. There were 3 discontinuations due to adverse events. Seventy-three percent (27/37) of patients receiving RBV had adverse events leading to RBV dose modification. The RBV-free RUBY-II study had no hemoglobin-associated adverse events. CONCLUSION: Treatment with OBV/PTV/r ± DSV ± RBV was well tolerated and patients with HCV GT1 or 4 infection and stage 4 or 5 CKD had high SVR12 rates, including patients with compensated cirrhosis and/or prior treatment experience.

Impact of geographic location on access to liver transplantation among ethnic minorities.

BACKGROUND: Recent reports have documented ethnic disparity in access to health care. This disparity appears to exist in organ transplantation and the contributing factors include lack of insurance as well as poor socioeconomic status. The role of geographic location and ethnic composition on accessibility to liver transplantation (LT) is unclear. Therefore, the aim of this study was to determine ethnic transplantation trends based on United Network for Organ Sharing (UNOS) regions. METHODS: Using the UNOS database, we identified all adults (> or =18 years) that received LT between 2000 and 2005. We excluded multiorgan transplants and living donor transplantation. The data collected included ethnicity, transplantation rate, and UNOS region. Data were analyzed using the chi test. RESULTS: A total of 30,311 patients received a LT during the study period. Of these, 22,673 (74.8%) were white, 3621 (12%) were Hispanic, 2490 (8.2%) were African Americans, and the rest of other ethnic groups (5%). Liver transplantation based on ethnicity was region specific, with the lowest for African Americans in region 6 (2.7%), for Hispanics in region 11 (2.2%), and for whites in region 5 (57.6%), respectively. There was no consistent correlation between the ethnicity of the recipients and the ethnic composition of the geographic location (region). CONCLUSION: Significant variations in access to liver transplantation for ethnic minorities exist across geographic lines. Understanding the interaction between ethnic minorities with end-stage liver disease in a geographic location and a transplant center will be invaluable as a first step in identifying the key nonmedical factors that play a role in this disparity.

Liver transplantation trends for older recipients: regional and ethnic variations.

BACKGROUND: Liver transplantation (LT) provides long-term survival for adults with end-stage liver disease. As a result of improved survival and an aging United States population the demand for LT in older patients is expected to increase. The aim of this study was to describe the transplantation trends in the older recipient (older than 65 years). METHODS: Using the United Network for Organ Sharing database, we identified LT recipients between 1990 and 2006. We used Kaplan-Meier method to calculate overall survival (1, 3, 5 and 10 years) and Cox regression for predictors of survival. RESULTS: During the study period 5630 (7.6%) LT recipients were older than 65 years. There were 4256 (79.4%) whites, Hispanic (10.3%), African Americans (AA) (3.6%), and rest (6.7%). There was an increase in LT for older than 65 years from 4.1% in 1990 to 10.2% in 2006 (P=0.002) and a regional variation (P<0.001). The 10-year patient and graft survival was 60% and 57% for less than 65 years versus 42% and 40% for more than 65 years (P<0.0001). With age stratification (65-75 years vs. >75 years), there was no difference in survival but when adjusted for race there was a significant difference in graft survival with a 10 year (white 40%, Hispanic 44%, and AA 19%) (P=0.04). CONCLUSION: The demand for LT in recipients older than 65 years is increasing. Although their survival is lower in comparison with recipients less than 65 years, there seems to be no difference in unadjusted survival with age stratification above 65 years. Among ethnic minorities, there was a disproportionately lower percentage of African Americans LT and a decreased survival.

Is Fulminant Hepatic Failure the Nemesis for Liver Transplant Centers? A Two Decade Psychosocial and Long-Term Outcome Study.

Long-term outcomes in liver transplantation for acute liver failure (ALF) are poorly studied. The aim of the study was to identify psychosocial variables that affect adherence and late survival. Retrospective review of ALF liver transplant (LTx) patients between 1997 and 2017 (n = 47) was conducted. Psychosocial history, life stressors, and ability to participate in transplant were recorded. Survival was calculated using Kaplan-Meier and logistic regression. Eleven patients (31.5%) had poor adherence, four died, all from graft failure. Of 13 with fair and 12 with good adherence, two died, no adherence related. Poor adherence was associated with higher mortality (P = 0.04), but by Kaplan-Meier, their five- and 10-year survival was 78 and 54 per cent, versus fair and good adherence (five years, 83% P = 0.3). Participating in transplant decision improved survival (five years, 80%) versus not participating (five years, 61%; P = 0.03). Of 10 early deaths, three were neurologic and five of sepsis. Overall, one- and five-year survival was 78 and 69 per cent. ALF represents the nemesis of LTx programs. Psychosocial aspects pre-LTx, stressors, and poor adherence affected survival in this series. No improvement over two decades of ALF LTxs was observed. The ethics of transplanting these high-risk patients will be the subject of our future research.

Outcomes of abdominal surgeries in cirrhotic patients performed by liver transplant surgeons: Are these safe?

BACKGROUND: Elective abdominal surgeries in patients with cirrhosis have been discouraged due to the high risk of complications. This study investigates the outcomes and safety of surgeries for hernias, and laparoscopic cholecystectomies in cirrhotic patients. METHODS: A retrospective cohort study that compared 91 cirrhotic patients to a control group of non-cirrhotic patients operated by liver transplant surgeons was conducted between 2009 and 2015. RESULTS: No statistical significance found in re-admission rates or complication rates (p = 0.21). Hernia recurrent rates were similar (p = 0.27). Survival rates among cirrhotic versus non cirrhotic group was 93.4% and 98.9% respectively (p = 0.0539). Amongst the 91 cirrhotic patients, there was a 100% survival rate for both ventral herniorrhaphies and laparoscopic cholecystectomy. Survival in umbilical and inguinal herniorrhaphies was 88.2% and 89.5% respectively. Mortality rate for umbilical and inguinal hernias was 11.7% and10.5% respectively. Mortality by Child-Pugh (CP) class were; 8.8% for CP B and 10.7% for CP class C. All CP class A patients survived. CONCLUSIONS: Our study indicates that elective operations could be performed safely with acceptable mortality in cirrhotic patients.