The Educational Impact of the Specialty Care Access Network–Extension of Community Healthcare Outcomes Program

Background: With the aging hepatitis C cohort and increasing prevalence of fatty liver disease, the burden on primary care providers (PCPs) to care for patients with liver disease is growing. In response, the Veterans Administration implemented initiatives for primary care-specialty referral to increase PCP competency in complex disease management. The Specialty Care Access Network?Extension of Community Healthcare Outcomes (SCAN-ECHO) program initiative was designed to transfer subspecialty knowledge to PCPs through case-based distance learning combined with real-time consultation. There is limited information regarding the initiative's ability to engage PCPs to learn and influence their practice. Materials and Methods: We surveyed PCPs to determine the factors that led to their participation in this program and the educational impact of participation. Results: Of 51 potential participants, 24 responded to an anonymous survey. More than 75% of respondents participated more than one time in a SCAN-ECHO clinic. Providers were motivated to participate by a desire to learn more about liver disease, to apply the knowledge gained to future patients, and to save their patients time traveling to another center for specialty consultation. Seventy-one percent responded that the didactic component and case-based discussion were equally important. It is important that participation changed clinical practice: 75% of providers indicated they had personally discussed the information they learned from the case presentations with their colleague(s), and 42% indicated they helped a colleague care for their patient with the knowledge learned during discussions of other participants' cases. Conclusions: This study shows that the SCAN-ECHO videoconferencing program between PCPs and specialists can educate providers in the delivery of specialty care from a distance and potentially improve healthcare delivery.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140279/1/tmj.2013.0302.pd

Nephrogenic systemic fibrosis associated with stromal and vascular calcification, report of two cases

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75035/1/j.1600-0560.2008.01205.x.pd

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

Contemporary outcomes and risk factors of acute graft-versus-host disease after liver transplant.

Introduction: Acute graft-versus-host-disease (GVHD) is a rare complication of orthotopic liver transplant (LT) that has an estimated incidence of 0.1%-2% per year. This complication of OLT carries a high mortality and affects the skin, gastrointestinal tract, and bone marrow. GVHD usually presents within 6 weeks after LT. There is limited data on GVHD after LT, and prior reported risk factors include: older age of recipient, HLA A and B matching, \u3e 20-year donor to recipient age difference, and alcoholic liver disease. We aimed to study outcomes of recent cases of acute GVHD after LT and explore potential risk factors due to the dearth of literature in this area. Methods: This is a retrospective, single center, review of patients who underwent LT between 2014-2016 and diagnosed with acute GVHD. GVHD was diagnosed both on clinical characteristics (fever, rash, diarrhea) as well as skin biopsy. Chimerism was tested on the skin biopsies. Descriptive statistics were utilized to analyze the outcomes and risk factors. Results: Seven patients were diagnosed with acute GVHD after LT during this time period. The mean time from transplant to diagnosis of GVHD was 42 days and all had a rash. The etiology of cirrhosis was 71% NASH, 14% Hepatitis C, and 14% alcoholic cirrhosis. An age gap of \u3e20 years was identified in 86% of our patients. All patient had positive chimerism in the skin. HLA matching was compared between the donor and recipient; specifically A, B, C, DR, DQA1 and DQB1. Zero shared class 1 alleles were noted in 43% of patients and 25% of those did not share a class 2 allele. Of the class II alleles, 86% had one or more common alleles with the donor. Topical steroids were used in 14% of cases. IV solumedrol was used in 86% of patients. Etanercept was used on 57% of the patients and 50% of those were were also treated with photophoresis. Death occurred in 43%. Conclusion: In our study, risk factors for acute GVHD patients included a greater than 20 year age difference and HLA crossmatch. The majority of our patients shared at least one class 1 allele with their donor, however, we have a significant amount of class 2 allele crossmatch. The number of shared alleles did not appear to correlate with risk of developing GVHD after LT or intensity of treatment required. With early recognition and more aggressive treatment options, our data suggests that mortality for acute GVHD after LT may be improving over time. This needs to be confirmed with larger studies

THE IMPLICATIONS OF CHRONIC OPIOID USE ON POST-TRANSPLANT CLINICAL OUTCOMES: A SYSTEMATIC REVIEW AND META-ANALYSIS

Background: Based on current literature, pre-transplant chronic opioid use (COU) for analgesia is highly prevalent among patients awaiting solid-organ transplant. However, there are very few large-scale studies on the effect of COU on post-transplant outcomes. We conducted a systematic review and meta-analysis to evaluate the impact of pre-transplant COU on solid-organ transplantation clinical outcomes. Methods: A comprehensive literature review was conducted by searching the PubMed, Ovid Medline, Embase, Web of Science, and Cochrane databases from inception to April 2020 to identify all studies that evaluated the impact of pre-transplant COU on post-transplant clinical outcomes. COU was defined as \u3e3 months of consecutive opioid use entering transplant listing. The search included studies regarding heart, lung, kidney, and liver transplantation. Our primary outcome was all-cause mortality, and secondary outcomes were graft failure and the one-year readmission rate. A random-effect model was used to estimate the pooled hazard ratios (HR) or odds ratios (OR) of our outcomes. Results: Nine retrospective studies involving 166,765 patients were included in the primary meta- analysis. The all-cause post-transplant mortality rate was significantly higher in patients who were on chronic opioids preceding transplant compared to those who were not (HR 1.42; 95% CI 1.34-1.50). The included studies demonstrated low heterogeneity (Figure 1, part A). Additionally, COU patients had an increased risk of graft failure compared to non-COU patients (HR 1.26; 95% CI (1.13-1.40) (Figure 1, part B). With regards to the one-year readmission rates, and noting that only three studies included data on readmission rates, there was no statistically significant difference in the readmission rate between the two groups (HR 1.78; 95% CI (0.87-3.63). The studies had high heterogeneity (Figure 1, part C). Conclusion: This study demonstrates that pre-transplant COU in solid-organ transplant patients is associated with an increased risk of all-cause mortality and graft failure. Pre- transplant COU may be a surrogate for comorbidities causing chronic pain or psychosocial traits that can contribute to non- compliance post-transplant. These potential risk factors may explain the increased risk of poor outcomes post-transplant. Therefore, a careful evaluation of opioid use patterns and consideration of alternative analgesic strategies is warranted in this population to lessen the reliance on opioid use and associated adverse outcomes

Portopulmonary Hypertension: A Survey of Practice Patterns and Provider Attitudes

Background: The role of liver transplantation (LT) in the management of portopulmonary hypertension (POPH) is poorly understood. The aim of this study was to better understand provider attitudes and practice patterns regarding the management of patients with POPH and to assess the concordance between clinical practice and current guidelines. Methods: We performed a multicenter survey study of hepatologists and pulmonary hypertension (PH) physicians at US LT centers that performed \u3e50 transplants per year. Survey responses are summarized as number (%). Associations were assessed using a Wilcoxon-rank sum, chi-square, or Fisher exact test, as appropriate. Results: Seventy-four providers from 35 centers were included. There was marked variability regarding screening practices, management, and attitudes. Forty-two percent responded that POPH nearly always or often improves with LT, and 15.5% reported that POPH rarely or never improves. In contrast to current guidelines, 50.7% agreed that treated POPH should be an indication for LT in patients with compensated cirrhosis. Hepatologists were more likely than PH physicians to agree that POPH should be an indication for LT (P = 0.02). Forty-nine percent of respondents thought that the current POPH Model for End-stage Liver Disease exception criteria should be modified, and management of patients with an elevated mean pulmonary arterial pressure and normal pulmonary vascular resistance differed from current policies. Conclusions: There is marked variability in provider attitudes and practice patterns regarding the management of POPH. This study highlights the need for prospective studies to inform practice and for improved implementation of practice guidelines in order to standardize care

Predictors of Waitlist Mortality in Portopulmonary Hypertension

BACKGROUND: The current Organ Procurement Transplantation Network policy grants Model for End-Stage Liver Disease (MELD) exception points to patients with portopulmonary hypertension (POPH), but potentially important factors, such as severity of liver disease and pulmonary hypertension, are not included in the exception score, and may affect survival. The purpose of this study was to identify significant predictors of waitlist mortality in patients with POPH. METHODS: We performed a retrospective cohort study of patients in the Organ Procurement and Transplantation Network database with hemodynamics consistent with POPH (defined as mean pulmonary arterial pressure \u3e25 mm Hg and pulmonary vascular resistance [PVR] ≥240 dynes·s·cm) who were approved for a POPH MELD exception between 2006 and 2014. Using a Cox proportional hazards model, we identified predictors of waitlist mortality (or removal for clinical deterioration). RESULTS: One hundred ninety adults were included. Age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.00-1.08; P = 0.0499), initial native MELD score (HR, 1.11; 95% CI, 1.05-1.17; P \u3c 0.001), and initial PVR (HR, 1.12 per 100 dynes·s·cm; 95% CI, 1.02-1.23; P = 0.02) were the only significant univariate predictors of waitlist mortality and remained significant predictors in a multivariate model, which had a c-statistic of 0.71. PVR and mean pulmonary arterial pressure were not significant predictors of posttransplant mortality. CONCLUSIONS: Both the severity of liver disease and POPH (as assessed by MELD and PVR, respectively) were significantly associated with waitlist, but not posttransplant, mortality in patients with approved MELD exceptions for POPH. Both factors should potentially be included in the POPH MELD exception score to more accurately reflect waitlist mortality risk

LIVER INJURY IS ASSOCIATED WITH INCREASED MORBIDITY AND MORTALITY IN COVID-19 PATIENTS

Background: Based on current literature there appears to be a high prevalence of liver injury (LI) in patients with COVID-19. However, there are limited large scale studies on risk factors, morbidity, and mortality associated with LI in these patients. We aim to determine risk factors and outcomes of patients hospitalized with COVID-19 and LI. Methods: We performed a retrospective single-center study at a large tertiary care hospital. All index admissions of adult patients with confirmed COVID19 between 3/1 to 4/30/2020 were included. Data on baseline characteristics and clinical outcomes was collected during manual chart review. Mild elevation in LFTs (MEL), defined as peak levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB) above upper limit of normal (ULN) but lower than the threshold for LI. LI was defined as peak ALT/AST three times ULN and/or peak ALP/TB two times ULN. ULN threshold values of ALT 52, AST 35, TB 1.2, ALP 140 were used. Both cohorts were compared with our control group, who had normal LFTs at presentation and throughout the hospitalization. SAS 9.4 was used for analysis. Results: A total of 1935 patients were included of which 507 (26.2%) had normal LFTs, 1030 (53.2%) had MEL, and 397 (20.5%) had LI. Males were more commonly found in the MEL (p=0.0004) and LI groups compared to control (p\u3c.0001). Patients in the MEL cohort were older (p=0.0005). African Americans were more likely to develop LI (p=0.0318). There was no difference in comorbidities between all groups. Among patients with LI, 241 (61%) had a hepatocellular pattern, 20 (5%) had a cholestatic pattern, and 135 (34%) had a mixed pattern. Patients with LI had an increased risk of mortality (RR 4.26 [95% CI 3.12, 5.81; p\u3c.0001]), ICU admission (RR 5.52 [95% CI 4.07, 7.49; p\u3c.0001]), intubation (RR 11.01 [95% CI 6.97, 17.34]); p\u3c.0001) and 30-day readmission (1.81 [95% CI 1.17, 2.80; p\u3c.0076]) (Table 2, Figure 1) compared to the control group. Conclusion: Our study demonstrates that patients with COVID-19 who present with LI have a significantly increased risk of mortality, mechanical ventilation, ICU admission, and 30-day re-admission compared to patients with MEL and normal LFTs. This information is important to appropriately manage COVID-19 patients. Further research looking at risk prediction models and pooling multi-center data should include liver injury as a key variable

Evaluation of Liver Transplantation Among Advanced Age Recipients in a Large Multicenter U. S. Cohort

Purpose: The proportion of adults \u3e70 years (y) listed for liver transplant (LT) in the U. S. is rising. Outcomes in this growing population are limited to small, single-center cohorts or national database studies that lack granularity. We aimed to better characterize outcomes in LT recipients \u3e70y in a large multicenter cohort. Methods: All primaty LT recipients (LTR) \u3e65y~who underwent LT from 2010-16 at 13 centers were included. For LTRs \u3e70y, survival was estimated using Kaplan-Meier methods; other outcomes were assessed within ly post-LT and compared toLTRs\u3c70y. Results: Of 179 LTRs \u3e70y, median was age 71y (range 70-78), 64% were male. and 770/c Caucasian. Leading indications for LT were NASH (27%), alcohol (11%). HCV (17%). 52% had HCC, of which 63% had MELD exceptions. Median laboratory MELDNa at LT was 19 (IQR 13-26), and median allocation MELD was 22 (IQR16-29). Comorbidities included diabetes (39%), congestive heart failure (8%), cerebrovascular disease (6%), chronic pulmonaty disease (11%), renal disease (38%). and osteoporosis/osteopenia (42%). The median donor age was 48y (33-62); 8% were donations after cardiac death, 10% living donation LT, and 6% SLK During LT, 1. 70/0 received induction with a T-cell depleting agent compared to 9% of LTRs \u3c70y in the cohort. At discharge, 77% were on calcineurin inhibitors and 73% on steroids vs 85% and 84% respectively, of LTRs \u3c70y. Within ly post-LT, graft rejection occurred in 18% and biliary strictures in 26%. Cardiovascular complications occurred in 25% (12% afib, 3% MI, 8% stroke and 9% heart failure), delirium in 16% and seizures in 3%. Viral, bacterial and fungal infections occurred ly post-LT in 17% 39% and 7% respectively. Solid organ cancers ly post-LT occurred in 10% with recurrent HCC (40/0) and lung cancer (2%) being the most common; this is compared to 4% in the cohort \u3c70y (p=0. 002). One-year and three-year patient survival was 89% and 76% respectively, vs 90% and 84% in \u3c70y. Conclusions: In a large US multicenter cohort, ly and 3y survival in LTRs \u3e70y were acceptable. De novo solid organ cancers within ly post-LT occurred in 10% of LTRs \u3e70y, more frequently than in those \u3c70y. Our data provide further understanding of the comorbidities experienced in advanced age LTRs and lay the foundation for improved selection and management of older LTRs

Association between sustained virological response and clinical outcomes in patients with hepatitis C infection and hepatocellular carcinoma

BACKGROUND: Sustained viral response (SVR) improves survival for patients with hepatitis C (HCV) and hepatocellular carcinoma (HCC) after curative treatment; however, the benefit of SVR in those with active HCC with a significant competing risk of mortality is unknown. This study aimed to evaluate the association between SVR and outcomes in patients with active HCC. METHODS: The authors performed a multicenter, retrospective cohort study including consecutive adults with HCV cirrhosis and treatment-naive HCC diagnosed between 2014 and 2018. Patients were stratified into two groups: active viremia (n = 431) and SVR before HCC diagnosis (n = 135). All patients underwent nonsurgical therapy as their initial treatment and were followed until liver transplantation, last follow-up, or death. The primary outcome was incident or worsening hepatic decompensation within 6 months and the secondary outcome was overall survival. All analyses used inverse probability of treatment weights (IPTW) to account for differences between the nonrandomized cohorts. RESULTS: Post-SVR patients had significantly lower odds of hepatic decompensation compared to viremic patients (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.06-0.59). Results were consistent among subgroups of patients with Child Pugh A cirrhosis (OR, 0.22; 95% CI, 0.04-0.77), Barcelona Clinic Liver Cancer stage B/C HCC (OR, 0.20; 95% CI, 0.04-0.65), and those receiving nonablative HCC therapies (OR, 0.21; 95% CI, 0.07-0.67). However, in IPTW multivariable Cox regression, SVR was not associated with improved survival (hazard ratio, 0.79; 95% CI, 0.56-1.12). CONCLUSIONS: Patients with HCV-related HCC and SVR are less likely to experience hepatic decompensation than viremic patients, suggesting patients with HCC who are undergoing nonsurgical therapies may benefit from DAA treatment