Utility of scores to predict alcohol use after liver transplant (lt): take them with a grain of salt.

BACKGROUND AIMS: The Sustained Alcohol use post-Liver Transplant (SALT) and the High-Risk Alcohol Relapse (HRAR) scores were developed to predict return to alcohol use after liver transplant (LT) for alcohol associated liver disease (ALD). METHODS: A retrospective analysis of deceased donor LT 10/2018 to 4/2022 was performed. All patients (pts) underwent careful pre-LT psychosocial evaluation. Data on alcohol use, substance abuse, prior rehabilitation, and legal issues were collected. Post-LT, all were encouraged to participate in rehabilitation programs and underwent interval phosphatidylethanol (PeTH) testing. Pts with ALD were stratified by < or > 6 month sobriety prior to listing. Those with <6 month were further stratified as acute alcoholic hepatitis (AH) by NIAAA criteria and non-AH. The primary outcome was utility of the SALT (<5 vs. ≥5) and HRAR (<3 vs. ≥3) scores to predict return to alcohol use (+PeTH) within 1 year after LT. RESULTS: Of the 365 LT, 86 had > 6 month sobriety and 85 had <6 month sobriety; 41 with AH and 44 non-AH. In those with AH, the mean time of abstinence to LT was 58 days, and 71% failed prior rehabilitation. Following LT, return to drinking was similar in the AH (24%) compared to <6M non-AH (15%) and >6M ALD (22%). Only 4% had returned to heavy drinking. The accuracy of both the SALT and HRAR scores to predict return to alcohol was low (accuracy 61-63%) with poor sensitivity (46% and 37%), specificity (67-68%), positive predictive value (22-26%) with moderate negative predictive value (NPV) (81-83%), respectively with higher NPVs (95%) in predicting return to heavy drinking. CONCLUSIONS: Both SALT and HRAR scores had good NPV in identifying patients at low risk for recidivism.

Utility of Lille Score in Predicting 30-Day Survival in Steroid-Treated Alcohol-Associated Hepatitis.

BACKGROUND/AIMS: In alcohol-associated hepatitis (AH), the Lille score is used to assess futility of steroids. However, the ability of the Lille score to predict 30-day survival in AH is not well-defined. Our aim is to compare the utility of the Lille score in predicting 30-day survival in those with AH treated with steroids. METHODS: Retrospective chart review of 882 patients hospitalized with AH from January 1st, 2012 through December 30th, 2019 was performed. Of these, 201 patients with severe AH met the threshold to receive steroids. Those with data to calculate Lille score < 0.45 on day 4 (n = 29) or 7 (n = 89) who continued steroids were compared to 83 patients with Lille scores ≥ 0.45 on day 4 (n = 18) or 7 (n = 65) who stopped steroids. The primary outcome was 30-day survival. For comparison, a contemporaneous matched control group was also analyzed of 110 patients who were hospitalized with severe AH, but did not receive steroids. RESULTS: In patients with Lille score < 0.45, survival was higher at 30-day when compared to those with Lille score ≥ 0.45 (94.9% vs. 80.72%; p = 0.002). The sensitivity, specificity, positive predictive value and negative predictive value of Lille score (< 0.45) to predict 30-day survival was 95%, 19%, 63%, and 73%, respectively. CONCLUSIONS: In severe AH, those with Lille score < 0.45 at day 4 or 7 have improved 30-day survival compared to those with Lille score ≥ 0.45. In those receiving steroids, Lille score has excellent sensitivity to predict 30-day survival but poor specificity.

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation.

OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

Variation in Racial Disparities in Liver Transplant Outcomes Across Transplant Centers in the United States.

Little is known about the role that transplant centers may play in perpetuating racial disparities after liver transplantation, which are unexplained by patient-level factors. We examined variation in between-center and within-center disparities among 34,114 Black and White liver transplant recipients in the United States from 2010 to 2017 using Scientific Registry of Transplant Recipient (SRTR) data. We used Cox proportional hazards models to calculate transplant center-specific Black-White hazard ratios and hierarchical survival analysis to examine potential effect modification of the race-survival association by transplant center characteristics, including transplant volume, proportion of Black patients, SRTR quality rating, and region. Models were sequentially adjusted for clinical, socioeconomic, and center characteristics. After adjustment, Black patients experienced 1.11 excess deaths after liver transplant per 100 person-years compared with White patients (95% confidence interval [CI], 0.65-1.56), corresponding to a 21% increased mortality risk (95% CI, 1.12-1.31). Although there was substantial variation in this disparity across transplant centers, there was no evidence of effect modification by transplant center volume, proportion of minority patients seen, quality rating, or region. We found significant racial disparities in survival after transplant, with substantial variation in this disparity across transplant centers that was not explained by selected center characteristics. This is the first study to directly evaluate the role transplant centers play in racial disparities in transplant outcomes. Further assessment of the qualitative factors that may drive disparities, such as selection processes and follow-up care, is needed to create effective center-level interventions to address health inequity.

eHealth literacy and web-based patient portal usage among kidney and liver transplant recipients.

Patient portals promote self-management, but require skills with electronic health information which can be measured by a patient's eHealth literacy. We aimed to describe eHealth literacy among a population of kidney transplant (KT) and liver transplant (LT) recipients and to investigate the relationship between eHealth literacy and Web-based patient portal utilization. We conducted phone surveys (August 2016-March 2017) among 178 KT and 110 LT recipients at two large transplant centers, including the eHealth Literacy Scale (eHEALS) and items assessing routine portal usage. Portal users were defined as routine if usage was every day, weekly, or monthly. The mean eHEALS score was 30.9 (SD: 5.4), and 45.4% routinely used the patient portal more than a few times per month. Routine users had higher eHealth literacy than non-routine users and non-users (31.97 vs. 29.97 vs. 28.20, p < .001). Routine users had higher eHealth literacy scores compared with non-users after adjusting for transplant organ type, age, educational level, employment status, mobile Internet access, and transplant center (OR: 1.10, 95% CI: 1.03-1.17). KT and LT recipients who routinely use patient portals have high eHealth literacy compared with other diseased populations, which should be leveraged by encouraging routine usage to improve post-transplant health and medication adherence.

Optimizing cancer care for hepatocellular carcinoma at a safety-net hospital: The value of a multidisciplinary disease management team.

BACKGROUND: Hepatitis C (HCV) is the primary etiology of hepatocellular carcinoma (HCC) in the US multidisciplinary disease management teams (DMT) that optimize oncologic care. The impact of DMT for HCC in safety-net hospitals is unknown. METHODS: Patients diagnosed with HCC from 2009 to 2016 at Grady Memorial Hospital (GMH) were included. The primary aim was to evaluate referrals to care, receipt of therapy, and overall survival (OS) after DMT formation. Screening patterns of HCV patients for HCC were also examined. RESULTS: Of 204 HCC patients, median age was 58 years, with 81% male, 83% black. 46% presented with stage 4 disease, 53% had treatment with median OS 9.8 months. DMT formation was associated with increased referrals to surgery (49% vs 30%; P = .02), liver-directed therapy (58% vs 31%; P = .001), and radiation (13% vs 3%; P = .019). Patients were also more likely to get treatment (59% vs 41%; P = .026), with improved median OS (30.7 vs 4.9 months; P < .001). DMT did not alter HCV screening for HCC (23%). HCV patients screened for HCC had earlier stage disease (P = .001). CONCLUSION: Implementation of a DMT at GMH is associated with increased HCC patients referred for/receiving treatment, as well as improved survival. Few patients with HCV at risk for HCC are screened, despite DMT. Future efforts should aim to establish screening programs for HCV patients at risk for HCC.

Racial, Ethnic, and Socioeconomic Disparities in Web-Based Patient Portal Usage Among Kidney and Liver Transplant Recipients: Cross-Sectional Study.

BACKGROUND: Kidney and liver transplant recipients must manage a complex care regimen after kidney transplant. Although the use of Web-based patient portals is known to improve patient-provider communication and health outcomes in chronic disease populations by helping patients manage posttransplant care, disparities in access to and use of portals have been reported. Little is known about portal usage and disparities among kidney and liver transplant recipients. OBJECTIVE: The aim of this study was to examine patient racial/ethnic, socioeconomic, and clinical characteristics associated with portal usage among kidney and liver transplant recipients. METHODS: The study included all adult kidney and liver transplant recipients (n=710) at a large academic transplant center in the Southeastern United States between March 2014 and November 2016. Electronic medical record data were linked with Cerner portal usage data. Patient portal use was defined as any portal activity (vs no activity) recorded in the Cerner Web-based portal, including viewing of health records, lab results, medication lists, and the use of secure messaging. Multivariable log-binomial regression was used to determine the patient demographic, clinical, and socioeconomic characteristics associated with portal usage, stratified by organ. RESULTS: Among 710 transplant recipients (n=455 kidney, n=255 liver), 55.4% (252/455) of kidney recipients and 48.2% (123/255) of liver recipients used the patient portal. Black patients were less likely to use the portal versus white patients among both kidney (57% black vs 74% white) and liver (28% black vs 55% white) transplant recipients. In adjusted multivariable analyses, kidney transplant recipients were more likely to use the portal if they had higher education; among liver recipients, patients who were white versus black and had higher education were more likely to use the portal. CONCLUSIONS: Despite studies showing that patient portals have the potential to benefit transplant recipients as a tool for health management, racial and socioeconomic disparities should be considered before widespread implementation. Transplant centers should include portal training and support to all patients to encourage use, given its potential to improve outcomes.

Neutrophil-to-lymphocyte ratio correlates with proinflammatory neutrophils and predicts death in low model for end-stage liver disease patients with cirrhosis.

The Model for End-Stage Liver Disease (MELD) score has reduced accuracy for liver transplantation (LT) wait-list mortality when MELD ≤ 20. Neutrophil-to-lymphocyte ratio (NLR) is a biomarker associated with systemic inflammation and may predict cirrhotic decompensation and death. We aimed to evaluate the prognostic utility of high NLR (≥4) for liver-related death among low MELD patients listed for LT, controlling for stage of cirrhosis. In a nested case-control study of cirrhotic adults awaiting LT (February 2002 to May 2011), cases were LT candidates with a liver-related death and MELD ≤ 20 within 90 days of death. Controls were similar LT candidates who were alive for ≥90 days after LT listing. NLR and other covariates were assessed at the date of lowest MELD, within 90 days of death for cases and within 90 days after listing for controls. There were 41 cases and 66 controls; MELD scores were similar. NLR 25th, 50th, 75th percentile cutoffs were 1.9, 3.1, and 6.8. NLR was ≥ 4 in 25/41 (61%) cases and in 17/66 (26%) controls. In univariate analysis, NLR (continuous ≥ 1.9, ≥ 4, ≥ 6.8), increasing cirrhosis stage, jaundice, encephalopathy, serum sodium, and albumin and nonselective beta-blocker use were significantly (P < 0.01) associated with liver-related death. In multivariate analysis, NLR of ≥1.9, ≥ 4, ≥ 6.8 were each associated with liver-related death. Furthermore, we found that NLR correlated with the frequency of circulating low-density granulocytes, previously identified as displaying proinflammatory properties, as well as monocytes. In conclusion, elevated NLR is associated with liver-related death, independent of MELD and cirrhosis stage. High NLR may aid in determining risk for cirrhotic decompensation, need for increased monitoring, and urgency for expedited LT in candidates with low MELD. Liver Transplantation 23 155-165 2017 AASLD.

Simeprevir and Sofosbuvir (SMV-SOF) for 12 Weeks for the Treatment of Chronic Hepatitis C Genotype 1 Infection: A Real World (Transplant) Hepatology Practice Experience.

OBJECTIVES: The combination of simeprevir (SMV) and sofosbuvir (SOF) was found to be well-tolerated with high sustained virologic response (SVR) rates in patients with genotype 1 chronic hepatitis C in clinical trials. Previous experience with hepatitis C virus (HCV) therapy has shown that patient tolerability and treatment efficacy described in controlled clinical trials did not necessarily mirror the "real world" experience. The goal of this study was to define SVR rates in a "real world" analysis and to explore predictors of treatment response with SMV and SOF. METHODS: This is a retrospective study examining the "real world" treatment of 170 patients with chronic HCV genotype 1 using the combination of SMV and SOF with or without ribavirin (RBV) for a fixed 12-week duration irrespective of prior interferon therapy, transplant status or fibrosis stage. Differences between SVR cohorts were analyzed by both intention-to-treat (ITT) and per protocol. RESULTS: The vast majority of patients were genotype 1a, 77% were cirrhotic in the non-LT group, and 35% of the entire cohort was African-American. Combination treatment with SMV and SOF in genotype 1 chronic HCV patients achieved an overall SVR rate at 12 weeks after completion of therapy (SVR12) of 78% by ITT and 86% by per protocol (84% in non-liver transplant (LT) patients and 89% in post-LT recipients). The presence of hepatocellular carcinoma was found to be a significant negative predictor of SVR12, whereas an undetectable week eight VL was a significant positive predictor of SVR in the entire cohort. CONCLUSIONS: Our data confirm excellent SVR outcomes with favorable safety and tolerability profiles in patients who carry many traditional high-risk features for non-response, including post-LT recipients and patients with advanced liver disease.

Changing prioritization for transplantation: MELD-Na, hepatocellular carcinoma exceptions, and more.

PURPOSE OF REVIEW: This article summarizes the landmark events that shaped current deceased donor liver allocation and distribution policy in the USA and to provide an update on recently approved and anticipated policy changes. RECENT FINDINGS: For liver transplant candidates with model for end-stage liver disease more than 11, the 'MELD-Na' equation incorporating serum sodium will be used for allocation starting January 2016. The 'delay and cap' policy for hepatocellular carcinoma delays the start of model for end-stage liver disease exception by 6 months and subsequently grants 28 points, with increases every 3 months thereafter up to a maximum score at 34 points. There is new guidance for exception petitions for neuroendocrine tumors, polycystic liver disease, and primary sclerosing cholangitis. New guidelines for selecting candidates for simultaneous liver-kidney transplant are being developed that may include a 'safety net' for liver-only recipients with posttransplant renal failure. In an effort to provide broader geographic sharing of livers than in the current distribution system, new larger geographic areas are being considered. SUMMARY: Recent policy changes were designed to reduce waitlist mortality, yet inclusion of outcomes measures in allocation and the use of larger geographic distribution units will likely guide future policy changes.

Hepatocellular carcinoma in patients listed for liver transplantation: Current and future allocation policy and management strategies for the individual patient.

Liver transplantation can provide definitive cure for patients with cirrhosis and hepatocellular carcinoma (HCC) when used appropriately. Advances in the management of HCC have allowed improved control of HCC while waiting for liver transplantation and new approaches to candidate selection particularly with regard to tumor burden and downstaging protocols. Additionally, there have been recent changes in allocation policy related to HCC in the U.S. that cap the HCC MELD exception at 34 points and implement a 6-month delay in a HCC MELD exception. This review examines the U.S. liver transplant allocation policy related to HCC, comprehensively details locoregional therapy options in HCC patients awaiting liver transplantation, and considers the impact of an increasing burden of HCC on future liver graft allocation policy.

Stage of cirrhosis predicts the risk of liver-related death in patients with low Model for End-Stage Liver Disease scores and cirrhosis awaiting liver transplantation.

The Model for End-Stage Liver Disease (MELD) score has reduced predictive ability in patients with cirrhosis and MELD scores ≤ 20. We aimed to assess whether a 5-stage clinical model could identify liver transplantation (LT) candidates with low MELD scores who are at increased risk for death. We conducted a case-control study of subjects with cirrhosis and MELD scores ≤ 20 who were awaiting LT at a single academic medical center between February 2002 and May 2011. Conditional logistic regression was used to evaluate the risk of liver-related death according to the cirrhosis stage. We identified 41 case subjects who died from liver-related causes with MELD scores ≤ 20 within 90 days of death while they were waiting for LT. The cases were matched with up to 3 controls (66 controls in all) on the basis of the listing year, age, sex, liver disease etiology, presence of hepatocellular carcinoma, and MELD score. The cirrhosis stage was assessed for all subjects: (1) no varices or ascites, (2) varices, (3) variceal bleeding, (4) ascites, and (5) ascites and variceal bleeding. The MELD scores were similar for cases and controls. Clinical states contributing to death in cases were: sepsis 49%, spontaneous bacterial peritonitis 15%, variceal bleeding 24%, and hepatorenal syndrome 22%. In a univariate analysis, variceal bleeding [odds ratio (OR) = 5.6, P = 0.003], albumin (OR = 0.5, P = 0.041), an increasing cirrhosis stage (P = 0.003), reaching cirrhosis stage 2, 3, or 4 versus lower stages (OR = 3.6, P = 0.048; OR = 7.4, P < 0.001; and OR = 4.1, P = 0.008), a sodium level < 135 mmol/L (OR = 3.4, P = 0.006), and hepatic encephalopathy (OR = 2.3, P = 0.082) were associated with liver-related death. In a multivariate model including the cirrhosis stage, albumin, sodium, and hepatic encephalopathy, an increasing cirrhosis stage (P = 0.010) was independently associated with liver-related death. In conclusion, assessing the cirrhosis stage in patients with low MELD scores awaiting LT may help to select candidates for more aggressive monitoring or for living or extended criteria donation.

A narrative review of supportive and end of life care considerations in advanced hepatocellular carcinoma.

BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths, and case numbers continue to rise in the United States. HCC carries a poor prognosis, and management requires a multidisciplinary approach. This narrative review aims to identify opportunities for further integration of palliative care (PC) in HCC care. Given the high symptom burden faced by patients with HCC, early PC consultation can be beneficial for patients. METHODS: A search of PubMed was conducted from inception of the database to March 1, 2023. The search was composed of keywords and controlled vocabulary terms for concepts related to palliative medicine and symptom management in the setting of HCC. KEY CONTENT AND FINDINGS: This narrative review finds that although PC has been integrated into HCC guidelines, partnerships between PC and hepatology are still nascent in clinical practice. Treatment-related barriers pose a challenge to timely integration of PC in the care of HCC patients; evaluation or listing for transplantation can be perceived as a barrier to PC consultation, and unpredictable clinical courses make prognostication challenging. Providers may hesitate to pursue PC referral due to a lack of consensus around the role of PC, and for those that are referred, timing of consultation remains an issue, especially for those who are potential liver transplant candidates. There are few studies of PC in HCC, limiting evidence-based recommendations that can be made regarding PC involvement in this patient population. CONCLUSIONS: While PC is not routinely integrated into HCC care, recent guideline recommendations and a growing number of studies may change this over time. Although further evidence is needed, PC and hepatology teams partnering together can explore ways to improve the care of this patient population. PC consultation early in HCC care could assist in management of symptom relief, psychosocial and spiritual support, and caregiver support. Effective communication will be required to set parameters for referral and clarify potential outcomes of consultation. Teams should be prepared for the challenges involved in a culture change and paradigm shift in clinical practice.