HIV-Positive Liver Transplant Does not Alter the Latent Viral Reservoir in Recipients With Antiretroviral Therapy-Suppressed HIV.

The latent viral reservoir (LVR) remains a major barrier to HIV-1 curative strategies. It is unknown whether receiving a liver transplant from a donor with HIV might lead to an increase in the LVR because the liver is a large lymphoid organ. We found no differences in intact provirus, defective provirus, or the ratio of intact to defective provirus between recipients with ART-suppressed HIV who received a liver from a donor with (n = 19) or without HIV (n = 10). All measures remained stable from baseline by 1 year posttransplant. These data demonstrate that the LVR is stable after liver transplantation in people with HIV. Clinical Trials Registration. NCT02602262 and NCT03734393.

HOPE in action: A prospective multicenter pilot study of liver transplantation from donors with HIV to recipients with HIV.

Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

Estimating the potential pool of uncontrolled DCD donors in the United States.

Organs from uncontrolled DCD donors (uDCDs) have expanded donation in Europe since the 1980s, but are seldom used in the United States. Cited barriers include lack of knowledge about the potential donor pool, lack of robust outcomes data, lack of standard donor eligibility criteria and preservation methods, and logistical and ethical challenges. To determine whether it would be appropriate to invest in addressing these barriers and building this practice, we sought to enumerate the potential pool of uDCD donors. Using data from the Nationwide Emergency Department Sample, the largest all-payer emergency department (ED) database, between 2013 and 2016, we identified patients who had refractory cardiac arrest in the ED. We excluded patients with contraindications to both deceased donation (including infection, malignancy, cardiopulmonary disease) and uDCD (including hemorrhage, major polytrauma, burns, and poisoning). We identified 9828 (range: 9454-10 202) potential uDCDs/y; average age was 32 years, and all were free of major comorbidity. Of these, 91.1% had traumatic deaths, with major causes including nonhead blunt injuries (43.2%) and head injuries (40.1%). In the current era, uDCD donors represent a significant potential source of unused organs. Efforts to address barriers to uDCD in the United States should be encouraged.

Validation of predictive models identifying patients at risk for massive transfusion during liver transplantation and their potential impact on blood bank resource utilization.

BACKGROUND: Intraoperative massive transfusion (MT) is common during liver transplantation (LT). A predictive model of MT has the potential to improve use of blood bank resources. STUDY DESIGN AND METHODS: Development and validation cohorts were identified among deceased-donor LT recipients from 2010 to 2016. A multivariable model of MT generated from the development cohort was validated with the validation cohort and refined using both cohorts. The combined cohort also validated the previously reported McCluskey risk index (McRI). A simple modified risk index (ModRI) was then created from the combined cohort. Finally, a method to translate model predictions to a population-specific blood allocation strategy was described and demonstrated for the study population. RESULTS: Of the 403 patients, 60 (29.6%) in the development and 51 (25.5%) in the validation cohort met the definition for MT. The ModRI, derived from variables incorporated into multivariable model, ranged from 0 to 5, where 1 point each was assigned for hemoglobin level of less than 10 g/dL, platelet count of less than 100 × 109 /dL, thromboelastography R interval of more than 6 minutes, simultaneous liver and kidney transplant and retransplantation, and a ModRI of more than 2 defined recipients at risk for MT. The multivariable model, McRI, and ModRI demonstrated good discrimination (c statistic [95% CI], 0.77 [0.70-0.84]; 0.69 [0.62-0.76]; and 0.72 [0.65-0.79], respectively, after correction for optimism). For blood allocation of 6 or 15 units of red blood cells (RBCs) based on risk of MT, the ModRI would prevent unnecessary crossmatching of 300 units of RBCs/100 transplants. CONCLUSIONS: Risk indices of MT in LT can be effective for risk stratification and reducing unnecessary blood bank resource utilization.

Steroid-sparing maintenance immunosuppression is safe and effective after simultaneous liver-kidney transplantation.

Optimization of maintenance immunosuppression (mIS) regimens in the transplant recipient requires a balance between sufficient potency to prevent rejection and avoidance of excessive immunosuppression to prevent toxicities and complications. The optimal regimen after simultaneous liver-kidney (SLK) transplantation remains unclear, but small single-center reports have shown success with steroid-sparing regimens. We studied 4184 adult SLK recipients using the Scientific Registry of Transplant Recipients, from March 1, 2002, to February 28, 2017, on tacrolimus-based regimens at 1 year post-transplant. We determined the association between mIS regimen and mortality and graft failure using Cox proportional hazard models. The use of steroid-sparing regimens increased post-transplant, from 16.1% at discharge to 88.0% at 5 years. Using multi-level logistic regression modeling, we found center-level variation to be the major contributor to choice of mIS regimen (ICC 44.5%; 95% CI: 36.2%-53.0%). In multivariate analysis, use of a steroid-sparing regimen at 1 year was associated with a 21% decreased risk of mortality compared to steroid-containing regimens (aHR 0.79, P = .01) and 20% decreased risk of liver graft failure (aHR 0.80, P = .01), without differences in kidney graft loss risk (aHR 0.92, P = .6). Among SLK recipients, the use of a steroid-sparing regimen appears to be safe and effective without adverse effects on patient or graft survival.

Liver transplantation and waitlist mortality for HCC and non-HCC candidates following the 2015 HCC exception policy change.

Historically, exception points for hepatocellular carcinoma (HCC) led to higher transplant rates and lower waitlist mortality for HCC candidates compared to non-HCC candidates. As of October 2015, HCC candidates must wait 6 months after initial application to obtain exception points; the impact of this policy remains unstudied. Using 2013-2017 SRTR data, we identified 39  350 adult, first-time, active waitlist candidates and compared deceased donor liver transplant (DDLT) rates and waitlist mortality/dropout for HCC versus non-HCC candidates before (October 8, 2013-October 7, 2015, prepolicy) and after (October 8, 2015-October 7, 2017, postpolicy) the policy change using Cox and competing risks regression, respectively. Compared to non-HCC candidates with the same calculated MELD, HCC candidates had a 3.6-fold higher rate of DDLT prepolicy (aHR = 3.49 3.69 3.89 ) and a 2.2-fold higher rate of DDLT postpolicy (aHR = 2.09 2.21 2.34 ). Compared to non-HCC candidates with the same allocation priority, HCC candidates had a 37% lower risk of waitlist mortality/dropout prepolicy (asHR = 0.54 0.63 0.73 ) and a comparable risk of mortality/dropout postpolicy (asHR = 0.81 0.95 1.11 ). Following the policy change, the DDLT advantage for HCC candidates remained, albeit dramatically attenuated, without any substantial increase in waitlist mortality/dropout. In the context of sickest-first liver allocation, the revised policy seems to have established allocation equity for HCC and non-HCC candidates.

Who can tolerate a marginal kidney? Predicting survival after deceased donor kidney transplant by donor-recipient combination.

The impact of donor quality on post-kidney transplant (KT) survival may vary by candidate condition. Characterizing this variation would increase access to KT without sacrificing outcomes. We developed a tool to estimate post-KT survival for combinations of donor quality and candidate condition. We studied deceased donor KT recipients (n = 120 818) and waitlisted candidates (n = 376 272) between 2005 and 2016 by using the Scientific Registry of Transplant Recipients. Donor quality and candidate condition were measured by using the Kidney Donor Profile Index (KDPI) and the Estimated Post Transplant Survival (EPTS) score. We estimated 5-year post-KT survival based on combinations of KDPI and EPTS score using random forest algorithms and waitlist survival by EPTS score using Weibull regressions. Survival benefit was defined as absolute reduction in mortality risk with KT. For candidates with an EPTS score of 80, 5-year waitlist survival was 47.6%, and 5-year post-KT survival was 78.9% after receiving kidneys with a KDPI of 20 and was 70.7% after receiving kidneys with a KDPI of 80. The impact of KDPI on survival benefit varied greatly by EPTS score. For candidates with low EPTS scores (eg, <40), the KDPI had limited impact on survival benefit. For candidates with middle or high EPTS scores (eg, >40), survival benefit decreased with higher KDPI but was still substantial even with a KDPI of 100 (>16 percentage points). Our prediction tool (www.transplantmodels.com/kdpi-epts) can support individualized decision-making on kidney offers in clinical practice.

Hepatitis C-positive donor liver transplantation for hepatitis C seronegative recipients.

BACKGROUND: The opioid crisis has led to an increase in hepatitis C virus-positive donors in the past decade. Whereas historically hepatitis C seropositive organs were routinely discarded, the advent of direct-acting antiviral agents has notably expanded the utilization of organs from donors with hepatitis C. There has been growing experience with liver transplantation (LT) from hepatitis C seropositive donors to hepatitis C seropositive recipients. However, data remain limited on LT from hepatitis C seropositive or hepatitis C ribonucleic acid positive donors to hepatitis C seronegative recipients. METHODS: We performed a retrospective study of 26 hepatitis C seronegative recipients who received hepatitis C seropositive donor livers followed by preemptive antiviral therapy with direct-acting antiviral treatment at the Johns Hopkins Hospital Comprehensive Transplant Center from January 1, 2017, to August 31, 2019. RESULTS: Twenty-five of the 26 recipients are alive with proper graft function; 20 of them received livers from hepatitis C nucleic acid testing positive donors. All 12 recipients who completed their direct-acting antiviral courses and have reached sufficient follow-up for sustained virologic response have achieved sustained virologic response. Nine of our recipients have either completed direct-acting antiviral treatment without sufficient follow-up time for sustained virologic response or are undergoing direct-acting antiviral treatment. One patient is awaiting antiviral treatment initiation pending insurance approval. Of note, 11 of 12 patients with sustained virologic response received a hepatitis C nucleic acid testing positive donor liver. CONCLUSION: Hepatitis C seronegative patients who receive a hepatitis C seropositive or hepatitis C nucleic acid testing positive liver allograft can enjoy good short-term outcomes with hepatitis C cure following direct-acting antiviral treatment.

MELD as a metric for survival benefit of liver transplantation.

Currently, there is debate among the liver transplant community regarding the most appropriate mechanism for organ allocation: urgency-based (MELD) versus utility-based (survival benefit). We hypothesize that MELD and survival benefit are closely associated, and therefore, our current MELD-based allocation already reflects utility-based allocation. We used generalized gamma parametric models to quantify survival benefit of LT across MELD categories among 74 196 adult liver-only active candidates between 2006 and 2016 in the United States. We calculated time ratios (TR) of relative life expectancy with transplantation versus without and calculated expected life years gained after LT. LT extended life expectancy (TR > 1) for patients with MELD > 10. The highest MELD was associated with the longest relative life expectancy (TR = 1.05 1.201.37 for MELD 11-15, 2.29 2.492.70 for MELD 16-20, 5.30 5.726.16 for MELD 21-25, 15.12 16.3517.67 for MELD 26-30; 39.26 43.2147.55 for MELD 31-34; 120.04 128.25137.02 for MELD 35-40). As a result, candidates with the highest MELD gained the most life years after LT: 0.2, 1.5, 3.5, 5.8, 6.9, 7.2 years for MELD 11-15, 16-20, 21-25, 26-30, 31-34, 35-40, respectively. Therefore, prioritizing candidates by MELD remains a simple, effective strategy for prioritizing candidates with a higher transplant survival benefit over those with lower survival benefit.

Organs from deceased donors with false-positive HIV screening tests: An unexpected benefit of the HOPE act.

Organs from deceased donors with suspected false-positive HIV screening tests were generally discarded due to the chance that the test was truly positive. However, the HIV Organ Policy Equity (HOPE) Act now facilitates use of such organs for transplantation to HIV-infected (HIV+) individuals. In the HOPE in Action trial, donors without a known HIV infection who unexpectedly tested positive for anti-HIV antibody (Ab) or HIV nucleic acid test (NAT) were classified as suspected false-positive donors. Between March 2016 and March 2018, 10 suspected false-positive donors had organs recovered for transplant for 21 HIV + recipients (14 single-kidney, 1 double-kidney, 5 liver, 1 simultaneous liver-kidney). Median donor age was 24 years; cause of death was trauma (n = 5), stroke (n = 4), and anoxia (n = 1); three donors were labeled Public Health Service increased infectious risk. Median kidney donor profile index was 30.5 (IQR 22-58). Eight donors were HIV Ab+/NAT-; two were HIV Ab-/NAT+. All 10 suspected false-positive donors were confirmed to be HIV-noninfected. Given the false-positive rates of approved assays used to screen > 20 000 deceased donors annually, we estimate 50-100 HIV false-positive donors per year. Organ transplantation from suspected HIV false-positive donors is an unexpected benefit of the HOPE Act that provides another novel organ source.

Racial differences in completion of the living kidney donor evaluation process.

Racial disparities in living donor kidney transplantation (LDKT) persist but the most effective target to eliminate these disparities remains unknown. One potential target could be delays during completion of the live donor evaluation process. We studied racial differences in progression through the evaluation process for 247 African American (AA) and 664 non-AA living donor candidates at our center between January 2011 and March 2015. AA candidates were more likely to be obese (38% vs 22%: P < .001), biologically related (66% vs 44%: P < .001), and live ≤50 miles from the center (64% vs 37%: P < .001) than non-AAs. Even after adjusting for these differences, AAs were less likely to progress from referral to donation (aHR for AA vs non-AA: 0.26 0.47 0.83; P = .01). We then assessed racial differences in completion of each step of the evaluation process and found disparities in progression from medical screening to in-person evaluation (aHR: 0.41 0.620.94; P = .02) and from clearance to donation (aHR: 0.28 0.510.91; P = .02), compared with from referral to medical screening (aHR: 0.78 1.021.33; P = .95) and from in-person evaluation to clearance (aHR: 0.59 0.931.44; P = .54). Delays may be a manifestation of the transplant candidate's social network, thus, targeted efforts to optimize networks for identification of donor candidates may help address LDKT disparities.

Clinicopathological Distinction of Low-AFP-Secreting vs. High-AFP-Secreting Hepatocellular Carcinomas.

Ilntroduction and aims. We aimed to investigate the clinical and pathological differences between low-AFP-secreting (AFP < 20 ng/mL) and high-AFP-secreting (AFP ≥ 20 ng/mL) hepatocellular carcinomas in patients who undergo liver transplant (LT). MATERIAL AND METHODS: We evaluated 145 patients who underwent deceased donor LT for HCC from January 1, 2005 until August 1, 2015 at the Johns Hopkins Hospital. RESULTS: Median pre-LT AFP in the entire cohort was 13 ng/mL (IQR 6-59). Using serum AFP cutoff of 20 ng/mL, 61 (42%) patients had high-AFP-secreting tumors and 84 (58%) had low-AFP-secreting tumors. Patients with high-AFP-secreting tumors had larger lesions (3 cm vs. 2.4 cm, p = 0.024), and were more likely to have microvascular-invasion (36.1% vs. 20.2%, p = 0.02) and poor-differentiation (18% vs. 4.8%, p = 0.01), and tumor recurrence following LT (28% vs. 6%, p < 0.001). The 1-year, 3-year, and 5-year recurrence-free survival for patients in the low-AFP-secreting group compared to the high-AFP-secreting group were 100%, 92%, 92% vs. 81.3%, 71.3%, 68.5% respectively (p = 0.0003). CONCLUSION: AFP is a suboptimal predictor of tumor recurrence following liver transplant in HCC patients. However, it can have some value in distinguishing more aggressive forms of HCC (high-AFP-secreting) that are associated with higher tumor recurrence. Novel tumor biomarkers are needed that can enhance predicting tumor recurrence following LT based on tumor biology.

Liver transplantation and cirrhotomimetic hepatocellular carcinoma: classification and outcomes.

Liver transplantation has become the standard-of-care treatment for hepatocellular carcinoma (HCC) that falls within certain size and numerical criteria for patients with cirrhosis. Cirrhotomimetic (CMM) HCC is an uncommon growth pattern that infiltrates cirrhotic parenchyma, can become extensive in size, and can evade detection via radiological studies. Liver transplant outcomes for this type of HCC are not well reported but generally are considered to be poor. We wished to better describe this variant of HCC in explanted livers, derive a classification system for this tumor type, and assess the outcomes of liver transplantation for this tumor variant. All patients undergoing transplantation for HCC at a single center in 1996-2009 (358 patients) were retrospectively analyzed, and 26 patients exhibiting a CMM growth pattern were identified. We developed a classification system for this tumor growth pattern variant and determined patient and tumor-specific outcomes. We derived a classification schema for CMM HCC based on the tumor extent and cellular histopathology, with a clear cell pathology being associated with favorable outcomes. We noted 100.0% 3-year recurrence-free survival and 58.3% 5-year recurrence-free survival after transplantation for those patients with tumors confined to 1 lobe that had a clear cell pathology and 16.2% 3- and 5-year recurrence-free survival for those patients who did not meet these criteria. In conclusion, CMM HCC features were noted in 7% of the patients undergoing transplantation for HCC at our center, with favorable outcomes observed for inpatients with clear cell histology and growth involving less than or equal to 50% of the liver.

Role of lower dose hepatitis B immune globulin prophylaxis in liver transplantation: A single center perspective.

Background and Aim: Prevention of hepatitis B virus (HBV) reinfection is important for long-term outcomes following liver transplantation (LT). Hepatitis B immunoglobulin (HBIG) is used among recipients who have (i) native HBV disease, (ii) hepatitis B core antibody positivity (HBcAb positivity), or (iii) received HBcAb positive organs. Nucleos(t)ide analogue (NA) monotherapy is emerging for treating patients in this setting. There is no generalized consensus on the ideal dosage of HBIG. The aim of this study was to evaluate the efficacy of low-dose HBIG (1560 international unit [IU]) for post-LT HBV prevention. Materials and Methods: HBcAb positive patients who received either HBcAb positive or hepatitis B core antibody negative (HBcAb negative) organs and HBcAb negative patients who received HBcAb positive organs between January 2016 and December 2020 were reviewed. Pre-LT HBV serologies were collected. HBV-prophylaxis strategy included NA with/without HBIG. HBV recurrence was defined as HBV deoxyribonucleic acid (DNA) positivity during the 1-year, post-LT follow-up. No HBV surface antibody titers were followed. Results: A total of 103 patients with a median age of 60 years participated in the study. Hepatitis C virus was the most common etiology. Thirty-seven HBcAb negative recipients and 11 HBcAb positive recipients with undetectable HBV DNA received HBcAb positive organs and underwent prophylaxis with 4 doses of low-dose HBIG and NA. None of the recipients in our cohort had a recurrence of HBV at 1 year. Conclusion: Low-dose HBIG (1560 IU) × 4 days and NA, for HBcAb positive recipients and HBcAb positive donors, appear to be effective in preventing HBV reinfection during the post-LT period. Further trials are needed to confirm this observation.

Donor BMI and Post-living Donor Liver Transplantation Outcomes: A Preliminary Report.

Living liver donor obesity has been considered a relative contraindication to living donation given the association with hepatic steatosis and potential for poor donor and recipient outcomes. We investigated the association between donor body mass index (BMI) and donor and recipient posttransplant outcomes. Methods: We studied 66 living donors and their recipients who underwent living donor liver transplant at our center between 2013 and 2020. BMI was divided into 3 categories (<25, 25-29.9, and ≥30 kg/m2). Magnetic resonance imaging-derived proton density fat fraction was used to quantify steatosis. Donor outcomes included length of stay (LOS), emergency department visits within 90 d, hospital readmissions within 90 d, and complication severity. Recipient outcomes included LOS and in-hospital mortality. The Student t test was used to compare normally distributed variables, and Kruskal-Wallis tests were used for nonparametric data. Results: There was no difference in donor or recipient characteristics based on donor BMI. There was no significant difference in mean magnetic resonance imaging fat percentage among the 3 groups. Additionally, there was no difference in donor LOS (P = 0.058), emergency department visits (P = 0.64), and hospital readmissions (P = 0.66) across BMI category. Donor complications occurred in 30 patients. There was no difference in postdonation complications across BMI category (P = 0.19); however, there was a difference in wound complications, with the highest rate being seen in the highest BMI group (0% versus 16% versus 37%; P = 0.041). Finally, there was no difference in recipient LOS (P = 0.83) and recipient in-hospital mortality (P = 0.29) across BMI category. Conclusions: Selecting donors with BMI ≥30 kg/m2 can result in successful living donor liver transplantation; however, they are at risk for perioperative wound complications. Donor counseling and perioperative strategies to mitigate wound-related issues should be used when considering obese living donors.

Patterns and kinetics of hepatocellular carcinoma relapse post-liver transplantation: oligorecurrence and role of local therapies.

Background: Amongst patients with recurrent hepatocellular carcinoma (HCC) post-liver transplantation, systemic therapy options may be limited by immunosuppression or poor performance status. Thus, we aimed to assess the impact of metastasis-directed therapy to all sites of disease (MDT-All) in HCC patients with limited disease recurrence [i.e., oligorecurrence (oligoM1)] post-transplantation and characterize pre-transplant characteristics associated with oligoM1. Methods: In this retrospective cohort study, patients at a single institution with recurrent HCC post-liver transplantation were identified. OligoM1 disease was defined as ≤3 lesions at recurrence, while polyrecurrent (polyM1) disease was defined as >3 lesions. Outcomes were compared in patients with oligoM1 disease by receipt of MDT-All. Regression analyses were used to identify predictors of polyM1 disease and characteristics associated with post-recurrence outcomes. Results: Forty-three patients with recurrent HCC post-liver transplantation from 2005-2022 were identified. Twenty-seven (63%) patients had oligoM1. Microvascular invasion was independently associated with polyM1 [odds ratio (OR): 14.64; 95% confidence interval (CI): 1.48-144.77; P=0.022]. Elevated alpha-fetoprotein (AFP) ≥400 ng/mL [hazard ratio (HR): 2.44; 95% CI: 1.08, 5.52; P=0.033] at recurrence was independently associated with inferior overall survival (OS), while oligoM1 (HR: 0.42; 95% CI: 0.21, 0.87; P=0.018) was independently associated with favorable OS. Amongst patients with oligoM1 who received MDT-All (n=15) median OS was 38.4 vs. 16.1 months for those who did not receive MDT-All (log-rank P=0.021). There was a non-significant improvement in polyprogression-free survival (polyPFS) (median 14.0 vs. 10.7 months, P=0.1) amongst oligoM1 patients who received MDT-All compared to those who did not. Conclusions: Receipt of MDT-All was associated with improved OS amongst patients with limited HCC disease recurrence following liver transplantation.

High Coronary Artery Calcium Score Is Associated With Increased Major Adverse Cardiac Events After Liver Transplantation.

Liver transplantation (LT) candidates frequently have multiple cardiovascular risk factors, and cardiovascular disease is a major cause of morbidity and mortality after LT. Coronary artery calcium (CAC) scores are a noninvasive assessment of coronary artery disease using computed tomography. This study examines CAC scores and cardiac risk factors and their association with outcomes after LT. Methods: Patients who underwent LT between January 2010 and June 2019 with a pretransplant CAC score were included in this study. Patients were divided by CAC score into 4 groups (CAC score 0, CAC score 1-100, CAC score 101-400, CAC score >400). Major adverse cardiovascular events (MACEs) were defined as myocardial infarction, stroke, revascularization, heart failure, atrial fibrillation, and cardiovascular death. Associations between CAC score and MACE or all-cause mortality within the 5-y post-LT follow-up period were analyzed using Cox regression. Statistical significance was defined as P < 0.05. Results: During the study period, 773 adult patients underwent their first LT, and 227 patients met our study criteria. The median follow-up time was 3.4 (interquartile range 1.9, 5.3) y. After 5 y, death occurred in 47 patients (20.7%) and MACE in 47 patients (20.7%). In multivariable analysis, there was no difference in death between CAC score groups. There was significantly higher risk of MACE in the CAC score >400 group, with a hazard ratio 2.58 (95% confidence interval 1.05, 6.29). Conclusions: CAC score was not associated with all-cause mortality. Patients with CAC score >400 had an increase in MACEs within the 5-y follow-up period compared with patients with a CAC score = 0. Further research with larger cohorts is needed to examine cardiac risk stratification in this vulnerable patient population.

Discovery and characterization of cross-reactive intrahepatic antibodies in severe alcoholic hepatitis.

The pathogenesis of antibodies in severe alcoholic hepatitis (SAH) remains unknown. We sought to determine if there was antibody deposition in SAH livers and whether antibodies extracted from SAH livers were cross-reactive against both bacterial antigens and human proteins. We analyzed immunoglobulins (Ig) in explanted livers from SAH patients (n=45) undergoing liver transplantation and tissue from corresponding healthy donors (HD, n=10) and found massive deposition of IgG and IgA isotype antibodies associated with complement fragment C3d and C4d staining in ballooned hepatocytes in SAH livers. Ig extracted from SAH livers, but not patient serum exhibited hepatocyte killing efficacy in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay. Employing human proteome arrays, we profiled the antibodies extracted from explanted SAH, alcoholic cirrhosis (AC), nonalcoholic steatohepatitis (NASH), primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), hepatitis B virus (HBV), hepatitis C virus (HCV) and HD livers and found that antibodies of IgG and IgA isotypes were highly accumulated in SAH and recognized a unique set of human proteins as autoantigens. The use of an E. coli K12 proteome array revealed the presence of unique anti- E. coli antibodies in SAH, AC or PBC livers. Further, both Ig and E. coli captured Ig from SAH livers recognized common autoantigens enriched in several cellular components including cytosol and cytoplasm (IgG and IgA), nucleus, mitochondrion and focal adhesion (IgG). Except IgM from PBC livers, no common autoantigen was recognized by Ig and E. coli captured Ig from AC, HBV, HCV, NASH or AIH suggesting no cross-reacting anti- E. coli autoantibodies. The presence of cross-reacting anti-bacterial IgG and IgA autoantibodies in the liver may participate in the pathogenesis of SAH.