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Background: Alcohol liver disease (ALD) may coexist with hepatitis C (HCV) in many transplant recipients (alcoholic cirrhosis with hepatitis C [AHC]). Our objective was to determine whether there were differences in postliver transplantation outcomes of patients with AHC when compared with those with alcoholic cirrhosis (AC) and/or alcoholic hepatitis (AH)., Methods: Using UNOS explant data sets (2016-2020), the survival probabilities of AC, AH, and AHC were compared by Kaplan-Meier survival analysis. Cox proportional-hazard regression analysis was used to determine outcomes after adjusting for disease confounders. The outcomes were also compared with predirect antiviral agent (DAA) period., Results: During study period, 8369 biopsy-proven ALD liver transplant recipients were identified. Of those, 647 had AHC (HCV + alcohol), 353 had AH, and 7369 had AC. MELD-Na score (28.7 ± 9.5 versus 23.8 ± 10.7; P  < 0.001) and presence of ACLF-3 (19% versus 11%; P  < 0.001) were higher in AC + AH as compared with AHC. AHC and AC+AH has similar adjusted mortality at 1-y, but 3-y (hazard ratios, 1.76; 95% confidence intervals, 1.32-2.35; P  < 0.0001) and 5-y (hazard ratios, 1.64; 95% confidence intervals, 1.24-2.15; P  = 0.0004) mortality rates were higher in AHC. Survival improved in the DAA era (2016-2020) compared with 2009 to 2013 in AHC, but remained worse in AHC group versus AC and/or AH. Malignancy-related mortality was higher in AHC (15% versus 9.3% in AC) in the DAA era., Conclusions: AHC was associated with lower 3- and 5-y post-LT survival as compared with ALD without HCV and the worse outcomes in AHC group continued in the DAA era., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Multiple listing (ML) at >1 transplant center is one mechanism to combat the geographic disparities in liver transplantation (LT) rates. The objective of our study was to determine the impact of multiple listing on LT rates., Methods: We examined the United Network of Organ Sharing database from 2002 to 2016 after excluding those listed for multiple organs, hepatocellular carcinoma, or living donor LT. The waitlist mortality and LT rates for the ML groups and the single listed (SL) group were compared after stratifying patients by the Model for End-Stage Liver Disease (MELD) with a cutoff at 15 (<15 and ≥15)., Results: Of the 83 935 listed during the study period, 80 351 were listed in a single center (SL group), and 3584 were listed in >1 center (ML group). Of the ML groups, 2028 (2.4%) were listed at multiple donor service areas but within the same region (ML-SR) and 1556 (1.9%) listed in different regions (ML-DR). The median MELD at LT was 20, 21, and 24 for ML-DR, ML-SR, and SL groups, respectively (P = 0.001). Although the probability of receiving LT was significantly higher for the ML groups relative to the SL group for both MELD groups (<15 and ≥15), the impact was the highest for ML-DR group. At MELD score <15, the probability of LT was 72% for ML-DR, 38% for ML-SR, and 32% for SL groups. At MELD score ≥15, the probability of LT was 79% for ML-DR, 67% for ML-SR, and 61% for SL groups., Conclusions: Multiple listing appeared to considerably improve a patient's chance of receiving LT and survival with the highest benefit for those with low MELD scores (<15) listed at multiple regions.

The real-world cure rates for hepatitis C (HCV) with direct-acting antivirals (DAAs) based on intention-to-treat (ITT) analysis may be lower than reported in the literature because of non-compliance.To determine whether patients treated in a structured outpatient HCV clinic (SHC) had higher compliance and treatment success rates compared to those treated in general hepatology clinics (GHC).In this study, we compared the treatment and compliance success rates of 488 and 840 patients treated in the SHC and GHC, respectively. The SHC required a pre-treatment clinic visit when patients picked up their initial medication, and received detailed education of the treatment plan and follow-up. In the GHC, the medications were delivered to patients' homes, and there was less formal education. Compliance success was defined as a combination of treatment completion and obtaining at least 1 post-treatment viral load at week 4 or 12. Treatment success was defined as either SVR4 or SVR12.Fifty of 488 (10.3%) patients from the SHC and 163 of 840 (19.4%) patients from the GHC were lost to follow-up (P < .0001). sustained virological response (SVR) rates were similar in compliant patients in both the SHC (419/438, 95.6%) and GHC (642/677, 94.8%), but treatment success rates by intention to treat (ITT) (overall 79.9%) were higher in SHC compared to GHC (85.9% vs 76.4%, P < .0001). Multivariate analysis showed that female patients (P = .01), older age (P = .0005), treatment in SHC (OR 1.7, 95% CI 1.2, 2.3, P = .0008), and sofosbuvir/simeprevir compared to sofosbuvir/ledipasvir had higher odds of compliance success; elbasvir/grazoprevir or dasabuvir/ombitasvir/paritaprevir/ritonavir had lower odds of compliance success compared to sofosbuvir/ledipasvir. Female patients (P = .02), older age (P < .0001), previous treatment (P = .03), treatment in SHC (OR 1.7, 95% CI 1.2, 2.3, P = .0008), and sofosbuvir/ledipasvir compared to sofosbuvir/velpatasvir, sofosbuvir, or elbasvir/grazoprevir had higher odds of treatment success. With 1:1 matching, the SHC group still had significantly higher odds than the GHC group of achieving treatment and compliance success.Our study shows that the effectiveness of HCV treatment could be improved by coordinating treatment in a structured HCV clinic.

Background: Nonalcoholic steatohepatitis (NASH) cirrhosis is a common indication for liver transplantation (LT) in the United States. There is a paucity of data on retransplantation (re-LT) in those who were initially transplanted for NASH., Methods: We queried the United Network for Organ Sharing data sets from 2002 to 2016 to analyze the outcomes of adults with NASH (n = 128) and compared them with groups that received re-LT for cryptogenic cirrhosis (n = 189), alcoholic cirrhosis (n = 300) or autoimmune hepatitis cirrhosis (n = 118) after excluding multiple-organ re-LT and individuals with hepatocellular carcinoma. We estimated survival probabilities using a Kaplan-Meier estimator, and a relative risk of patient and graft mortality using proportional hazards regression., Results: The NASH group was older and had a higher prevalence of obesity, type II diabetes mellitus, renal insufficiency, portal vein thrombosis, and poor performance status. The median interval between the first and the second LT was shorter in the NASH group (27 days). The graft and patient 5-year survival rates were lower for the NASH group after re-LT compared with the other 3 groups. After adjusting for demographic and disease complication factors, the factors that increased a risk of patient or graft failure were a poor performance status (hazard ratio [HR], 1.64; 1.19-2.26), Donor Risk Index (HR, 1.51; 1.08-2.12), and a high Model for End-stage Liver Disease score (HR, 1.02; 1.00-1.04)., Conclusions: Despite the comparable outcomes reported for initial LT among the various etiologies, the outcome of re-LT is significantly worse for NASH cirrhosis.

Background: Patients with nonalcoholic steatohepatitis (NASH) cirrhosis have excellent postliver transplant survival despite having many comorbidities. We hypothesized that this could be due to a selection bias., Methods: We analyzed the United Network for Organ Sharing data from 2002 to 2016 and compared postliver transplant survival of NASH (n = 7935) patients with cryptogenic cirrhosis (CC) (n = 6087), alcoholic cirrhosis (AC) (n = 16 810), and autoimmune hepatitis cirrhosis (AIH) (n = 2734)., Results: By 3 years of listing, the cumulative incidence (CI) of death or deterioration was 29% for NASH, 28% for CC and AC, and 24% for AIH, but when adjusted for risk factors, the CI was similar for NASH and AIH. The factors that increased the risk of waiting list removal due to death/deterioration were poor performance status, encephalopathy, diabetes, high Model for End-stage Liver Disease, Hispanic race, older age and a low serum albumin. Most patients were transplanted within the first year (median, 2 months; interquartile range, 1-7 months) of listing and by 5 years, the unadjusted CI of transplantation was 54% for NASH, 52% for CC, 51% for AIH, and 48% for AC. The adjusted CI of transplantation within 2 months of listing was higher for AC (subhazard ratio [SHR], 1.17), AIH (SHR, 1.17), and CC (SHR, 1.13) when compared with NASH, but after 2 months, adjusted transplantation rates decreased in AC (SHR, 0.6), AIH (SHR, 0.78), and CC (SHR, 0.95). The negative predictors of receiving a transplant were dialysis, female sex, nonwhite race, high albumin, and creatinine., Conclusions: Patients with NASH cirrhosis are not disadvantaged by higher waitlist removal or lower transplantation rates.

Background: The outcomes of liver transplantation (LT) in patients with cryptogenic cirrhosis (CC) have not been adequately examined except for small case series. We believe that patients currently listed as CC have truly cryptogenic liver disease and may have different post-LT outcomes compared with nonalcoholic steatohepatitis (NASH)., Methods: We compared the post-LT outcomes of adults with CC (n = 3241) and compared them with cirrhosis from NASH (n = 4089), alcoholic cirrhosis (AC) (n = 7837), and autoimmune hepatitis (AIH) (n = 1435) using the United Network for Organ Sharing database from 2002 to 2016. We excluded those who had multiorgan transplantation and hepatocellular carcinoma. In addition to the well-known predictors of liver transplant outcomes, we analyzed the impact of Karnofsky Performance Status score at LT on immediate and late outcomes., Results: There were significant differences in clinical characteristics between the groups. Despite these differences in clinical characteristics and risk factors, CC had similar graft and patient survival to NASH, AC, and AIH when assessed by Kaplan-Meier survival. Multivariate Cox regression analysis showed that graft and patient survival was similar in all 4 groups after adjusting for other confounders. Hispanics had a 24% lower risk of death (hazard ratio, 0.76) compared with whites in these combined cohorts after adjusting for all risk factors. In addition to other known risk factors, Karnofsky Performance Status score of 30% or less was associated with a 33% increase in risk of death (hazard ratio, 1.33) on multivariate analysis., Conclusion: Patients with CC had similar graft and patient survival when compared with NASH, AC, and AIH cirrhosis.

Objective: To quantify the independent association between obesity and access to liver transplantation., Background: Obesity is associated with higher complication rates, longer hospitalization, and worse survival after liver transplantation. Nevertheless, transplantation provides survival benefit to patients with end-stage liver disease, regardless of body mass index (BMI). We hypothesized that, despite survival benefit, providers were reluctant to transplant obese patients because of the inherent difficulty of these cases and their inferior outcomes. Our goal was to quantify the independent association between BMI and waiting time for orthotopic liver transplantation as a surrogate marker for this reluctance., Methods: We studied 29,136 wait-list candidates in the model for end-stage liver disease (MELD) era, categorized as severely obese (BMI 35-40), morbidly obese (BMI 40-60), and reference (BMI 18.5-35). All models were adjusted for factors relevant to the allocation system, factors possibly influencing access to healthcare, and factors biologically related to disease progression and outcomes., Results: The odds of receiving a MELD exception were 30% lower in severely obese and 38% lower in morbidly obese patients. Similarly, the likelihoods of being turned down for an organ were 10% and 16% higher, and the rates of being transplanted were 11% and 29% lower in severely obese and morbidly obese patients, respectively., Conclusions: Current practice seems to indicate a reluctance to transplant obese patients. If indeed as a community we feel that liver allografts should not be distributed to patients with excessive postoperative risk, we should consider expressing this as a formal change to our allocation policy rather than through informal practice patterns.

Background and Aim: Budd-Chiari syndrome (BCS) is a rare condition associated with hepatic venous outflow obstruction classically treated with portosystemic shunts or liver transplantation. Recent reports indicate promising results with the use of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of these patients., Patients and Methods: We reviewed a 10-year single-institution experience with TIPS in patients diagnosed with BCS., Results: Eleven patients with BCS underwent TIPS procedures, 3 of whom carried a diagnosis of paroxysmal nocturnal hemoglobinuria, a relative contraindication for liver transplantation. One TIPS procedure was unsuccessful for technical reasons. No patient suffered mortality or major morbidity related to the TIPS procedure. The mean reduction of portal venous pressures was 43.7%, with a mean decrease of 73% in the pressure gradient. Of the 7 patients where long-term follow-up was available, 57% had shunts which remained patent but required several nonsurgical revisions for occlusion, with an average assisted patency of 37.5 months., Conclusions: TIPS is an effective modality in the treatment of patients with BCS, especially for those who are not candidates for liver transplantation. TIPS can be successfully used as a bridge to surgical portosystemic shunting, as well as liver transplantation, but may cause technical difficulties when performing transplantation.

Transcatheter arterial chemoembolization is considered the mainstay of therapy for unresectable hepatocellular carcinoma. The purpose of this study was to assess the impact of such treatment on survival by performing a metaanalysis of all available randomized clinical trials comparing this form of therapy to supportive care. A MEDLARS search was conducted covering the years 1970 to 2002. Data analysis was performed according to methods described by Peto. The primary outcome of interest was the proportion of patients surviving 3 and 6 months after treatment. All analyses were performed on an intent-to-treat basis. A literature search yielded 1,100 citations, from which four met protocol-specified inclusion criteria. All studies contained an experimental and control arm totalling 268 patients. The odds ratio for 3- and 6-month survival were 1.31 (95% CI: 0.66-2.58) and 0.91 (95% CI: 0.49-1.68), which was not statistically significant. These data fail to show a survival advantage associated with therapeutic embolization versus supportive care alone in patients with unresectable hepatocellular carcinoma. Existing survival data from randomized controlled trials are of poor quality, and the paucity of patients in these trials eliminates the possibility of drawing meaningful conclusions regarding the effect of chemoembolization on patient survival from these studies.

Background: It is not known whether there was a difference in outcome between insulin-dependent diabetes mellitus (type 1) and non-insulin dependent diabetes mellitus (type 2) after liver transplantation., Methods: The outcome of liver transplantation in adult patients with type 1 (n=1,629) and type 2 (n=1,618) was compared to those without diabetes mellitus (DM) (nondiabetics, n=17,974) using the United Network for Organ Sharing database from 1994 to 2001, after excluding patients who had living donor or multiple organs or who underwent retransplantation, and those with incomplete data., Results: Cryptogenic cirrhosis, hypertension, and coronary artery disease (CAD) were two to three times more common in types 1 and 2 compared with nondiabetics. Five-year patient and graft survivals by Kaplan-Meier analysis were significantly lower for type 1 (P <0.0001) compared with type 2 or nondiabetics; only patient survival was lower for type 2 ( P=0.04). Cox regression survival analysis, after adjusting for confounding variables, showed a lower 1-year, 2-year, and 5-year patient and graft survival in patients with type 1 compared with nondiabetics; however, type 2 was not an independent predictor of survival. Preexisting CAD, and not hypertension, was also an independent predictor of poor 5-year survival. Patients who had both DM and CAD had a lower survival compared with those with either DM or CAD., Conclusions: Type 1 and CAD are both independent predictors of poor outcome after liver transplantation. Liver transplant recipients with type 1 or CAD have approximately 40% lower 5-year survival compared with patients without DM or CAD.

Background: The spectrum of disease caused by Ehrlichia spp. ranges from asymptomatic to fatal. Awareness and early diagnosis of the infection is paramount because appropriate therapy leads to rapid defervescence and cure. If left untreated, particularly in immunosuppressed patients, ehrlichioses may result in multi-system organ failure and death., Methods: We report the second case of human monocytic ehrlichiosis (HME) in a liver transplant recipient, and review the literature., Results: The patient presented with fever and headache, had negative cultures, and despite broad-spectrum antimicrobial coverage appeared progressively septic. After eliciting a history of tick exposure we treated the patient empirically with doxycycline. The diagnosis of HME was confirmed by 1) polymerase chain reaction (PCR) for Ehrlichia chaffeensis, 2) acute and convalescent serum titers, and 3) in vitro cultivation of E chaffeensis from peripheral blood., Conclusion: Although human ehrlichioses are relatively uncommon, they are emerging as clinically significant arthropod-borne infections. Although epidemiological exposure is responsible for infection, immunosuppression makes patients more likely to succumb to disease. A high index of suspicion and early treatment results in a favorable outcome.