Alcohol Use in Liver Transplant Recipients With Alcohol-related Liver Disease: A Comparative Assessment of Relapse Prediction Models.

BACKGROUND: The selection of liver transplant (LT) candidates with alcohol-related liver disease (ALD) is influenced by the risk of alcohol relapse (AR), yet the ability to predict AR is limited. We evaluate psychosocial factors associated with post-LT AR and compare the performance of high-risk alcoholism risk (HRAR), sustained alcohol use post-LT (SALT), and the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) scores in predicting relapse. METHODS: A retrospective analysis of ALD patients undergoing LT from 2015 to 2021 at a single US transplant center was performed. Risk factors associated with post-LT AR were evaluated and test characteristics of 3 prediction models were compared. RESULTS: Of 219 ALD LT recipients, 23 (11%) had AR during a median study follow-up of 37.5 mo. On multivariate analysis, comorbid psychiatric illness (odds ratio 5.22) and continued alcohol use after advice from a health care provider (odds ratio 3.8) were found to be significantly associated with post-LT AR. On sensitivity analysis, SIPAT of 30 was optimal on discriminating between ALD LT recipients with and without post-LT AR. SIPAT outperformed both the HRAR and SALT scores (c-statistic 0.67 versus 0.59 and 0.62, respectively) in identifying post-LT AR. However, all scores had poor positive predictive value (<25%). CONCLUSIONS: AR after LT is associated with comorbid psychiatric illness and lack of heeding health care provider advice to abstain from alcohol. Although SIPAT outperformed the HRAR and SALT scores in predicting AR, all are poor predictors. The current tools to predict post-LT AR should not be used to exclude LT candidacy.

Test performance metrics for breast, cervical, colon, and lung cancer screening: a systematic review.

BACKGROUND: Multiple quality metrics have been recommended to ensure consistent, high-quality execution of screening tests for breast, cervical, colorectal, and lung cancers. However, minimal data exist evaluating the evidence base supporting these recommendations and the consistency of definitions and concepts included within and between cancer types. METHODS: We performed a systematic review for each cancer type using MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 2010 to April 2020 to identify guidelines from screening programs or professional organizations containing quality metrics for tests used in breast, cervical, colorectal, and lung cancer screening. We abstracted metrics' definitions, target performance levels, and related supporting evidence for test completeness, adequacy (sufficient visualization or collection), accuracy, and safety. RESULTS: We identified 11 relevant guidelines with 20 suggested quality metrics for breast cancer, 5 guidelines with 9 metrics for cervical cancer, 13 guidelines with 18 metrics for colorectal cancer (CRC), and 3 guidelines with 7 metrics for lung cancer. These included 54 metrics related to adequacy (n = 6), test completeness (n = 3), accuracy (n = 33), and safety (n = 12). Target performance levels were defined for 30 metrics (56%). Ten (19%) were supported by evidence, all from breast and CRC, with no evidence cited to support metrics from cervical and lung cancer screening. CONCLUSIONS: Considerably more guideline-recommended test performance metrics exist for breast and CRC screening than cervical or lung cancer. The domains covered are inconsistent among cancers, and few targets are supported by evidence. Clearer evidence-based domains and targets are needed for test performance metrics. REGISTRATION: PROSPERO 2020 CRD42020179139.

Biopsy of Non-tumor Sites After Biopsy of a Colorectal Cancer is not Associated With Metachronous Cancers: A Case-control Study.

BACKGROUND & AIMS: Recent research has demonstrated biologic plausibility for iatrogenic tumor seeding via colonoscopy as a cause of metachronous colorectal cancers (CRC). This study evaluated the association between biopsy of non-tumor sites after CRC biopsy and risk of metachronous CRC in a large community-based health care organization. METHODS: This was a retrospective case-control study of adults with an initial CRC diagnosed by colonoscopy between January 2006 and June 2018 who underwent curative resection. Cases developed a second primary (metachronous) CRC diagnosed 6 months to 4 years after the initial CRC, and were matched by age, sex, diagnosis of inflammatory bowel disease, race, and ethnicity with up to 5 controls without a second CRC diagnosis. The exposure was biopsy in the colonic segment of the metachronous CRC (or corresponding segment in controls) after tumor biopsy, ascertained with blinding to case status. Associations were evaluated using conditional logistic regression and adjusted for potential cofounders. RESULTS: Among 14,119 patients diagnosed with an initial CRC during colonoscopy, 107 received a second CRC diagnosis. After exclusions for recurrent or synchronous CRC, 45 cases and 212 controls were included. There was no significant association between biopsy of non-tumor sites after initial CRC biopsy and risk of metachronous CRC in the segment of the additional biopsy site (adjusted odds ratio, 2.29; 95% confidence interval, 0.77-6.81). CONCLUSIONS: Metachronous cancers are not significantly associated with biopsy of non-tumor sites after biopsy of the primary cancer. Although the sample size does not allow definite exclusion of any association, these findings do not support iatrogenic tumor seeding as a common risk factor for metachronous CRC.

Percutaneous Ultrasound-Guided Kidney Transplant Biopsy Outcomes: From the Nephrologist to the Radiologist Standpoint.

Background: Kidney transplant biopsies are the gold standard for evaluating allograft dysfunction. These biopsies are performed by nephrologists and radiologists under real-time ultrasound guidance. A few studies have examined the outcomes of ultrasound-guided kidney transplant biopsy in transplant recipients; however, none have compared these outcomes between both specialties. Methods: We retrospectively analyzed a cohort of 678 biopsies performed in a single center during a 44-month study period. Biopsies were stratified into two groups based upon the specialist performing the procedure: interventional radiology (IR; N=447) and transplant nephrology (TN; N=231). Results: There were 55 (8%) complications related to biopsies in the entire cohort: 37 (8.2%) in the IR group and 18 (7.7%) in the TN group, without statistical difference between the groups (P=0.94). Blood pressure control and prior use of anticoagulation were significant predictors of complicated biopsies (P=0.004 and 0.02, respectively). Being a woman and prior use of anticoagulation were significant predictors of transfusion of blood products (P=0.01 and 0.01, respectively). Being a woman and blood pressure control were significant predictors of overall perinephric hematoma (P=0.01 and 0.01, respectively), and Black race was a significant predictor of perinephric hematoma without worsening of renal function (P=0.005). The specialist team performing the procedure was not a statistically significant predictor of biopsy complications, transfusion of blood products, or perinephric hematoma with comparable sample yield. Conclusions: Percutaneous ultrasound-guided kidney transplant biopsy performed by transplant nephrologists have similar complication rates when compared with interventional radiologists in an academic center.

Ethical and allocation issues in liver transplant candidates with alcohol related liver disease.

In the past decade, alcohol-related liver disease (ALD) has become the leading indication for liver transplantation (LT) in the United States. Despite this major development, there still remains some controversy in a distinct subset of this patient population, those presenting with alcoholic hepatitis (AH). There is significant debate within the transplant community regarding acceptance criteria for patients with AH requiring LT, especially those with less than 6 months of sobriety. With that being said, LT in the setting of ALD and AH has shown an improvement in survival rates; additionally, many studies have reported that careful selection of patients with ALD has produced excellent post-transplant outcomes even if transplant occurred with less than 6 months of sobriety. In this review, we aim to discuss the ethical and allocation-associated issues that arise when considering ALD and/or AH for LT; furthermore, we delve into the history, controversies, current guidelines, and future directions of LT in this subgroup.

Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation.

BACKGROUND & AIMS: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival. METHODS: We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis. RESULTS: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001). CONCLUSION: Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH. LAY SUMMARY: Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.

Targeting acid ceramidase inhibits YAP/TAZ signaling to reduce fibrosis in mice.

Hepatic stellate cells (HSCs) drive hepatic fibrosis. Therapies that inactivate HSCs have clinical potential as antifibrotic agents. We previously identified acid ceramidase (aCDase) as an antifibrotic target. We showed that tricyclic antidepressants (TCAs) reduce hepatic fibrosis by inhibiting aCDase and increasing the bioactive sphingolipid ceramide. We now demonstrate that targeting aCDase inhibits YAP/TAZ activity by potentiating its phosphorylation-mediated proteasomal degradation via the ubiquitin ligase adaptor protein ß-TrCP. In mouse models of fibrosis, pharmacologic inhibition of aCDase or genetic knockout of aCDase in HSCs reduces fibrosis, stromal stiffness, and YAP/TAZ activity. In patients with advanced fibrosis, aCDase expression in HSCs is increased. Consistently, a signature of the genes most down-regulated by ceramide identifies patients with advanced fibrosis who could benefit from aCDase targeting. The findings implicate ceramide as a critical regulator of YAP/TAZ signaling and HSC activation and highlight aCDase as a therapeutic target for the treatment of fibrosis.

Outcomes After Direct-Acting Antiviral Therapy Based on Donor Hepatitis C Serostatus Among Hepatitis C Virus-Infected Kidney Transplant Recipients.

OBJECTIVES: Renal grafts from hepatitis C virus-positive deceased donors, which were once discarded, can now be transplanted into recipients and treated posttransplant due to the emergence of direct-acting antivirals, significantly improving wait list time and organ shortages. Here, we compared outcomes in hepatitis C virus-positive patients who received kidneys from hepatitis C virus-positive versus -negative donors. MATERIALS AND METHODS: In this single-center retrospective study, we divided 52 kidney transplant recipients who were viremic for hepatitis C virus pretransplant into 2 groups based on donors' hepatitis C virus serostatus (positive/negative). Demographics, time to transplant, efficacy of direct-acting antivirals, rejection episodes, immunosuppression adjustments, and renal function were assessed in both groups. RESULTS: Our cohort included 50 patients receiving kidneys from deceased donors and 2 from living donors (1 related, 1 unrelated). Recipients of hepatitis C virus-positive kidneys had significantly less wait list time (36 days) than recipients of hepatitis C virus-negative kidneys (806 days; P < .001). All recipients responded well to direct-acting antivirals, with both groups showing similar sustained virologic response rates that were comparable to the general population. Intention-to-treat analyses showed rates of 91% and 100% in donor seropositive and donor seronegative groups, respectively (P = .273). Four antibody-mediated rejection episodes occurred in the donor seropositive and one mixed rejection in the donor seronegative group. Tacrolimus dose adjustments were required in 54% and 59% of recipients in the donor seropositive and seronegative groups, respectively. Recipients in the donor seropositive group had lower rates of worsening renal function than recipients in the donor seronegative group (11% vs 17.5%; P = .519). CONCLUSIONS: In hepatitis C-positive recipients with donor negative or donor positive hepatitis C virus serostatus, response of direct-acting antiviral response was not significantly different and renal allograft function was maintained without any evidence of long-term adverse consequences to the graft.

Computed Tomography-Guided Kidney Transplant Biopsy Outcomes: A Single-Center Experience.

OBJECTIVES: Percutaneous kidney transplant biopsy is typically performed using ultrasonographic guidance; computed tomography is an alternative modality used to obtain kidney allografttissuewhen ultrasonographyguided percutaneous kidney transplant biopsy is technically challenging. Studies examining postbiopsy outcomes in kidney transplant patients using a computed tomography-guided approach are scarce. Our goal was to reportthe incidence of nonsevere and severe complications in computed tomographyguided percutaneous kidney transplant biopsies and the potential risk factors. MATERIALS AND METHODS: We retrospectively reviewed computed tomography-guided percutaneous kidney transplant biopsies in patients undergoing work-up for kidney allograft rejection between 2013 and 2017. Demographics, comorbidities, laboratory data, history of antiplatelet and/or anticoagulant use, and complications were assessed. RESULTS: : During the study period, 28 patients underwent computed tomography-guided percutaneous kidney transplant biopsies; mean age was 57.5 ± 15.5 years, and 12 (43%)werewomen.Twenty-three patients (82%) were obese, with a body mass index greater than 30 kg/m². Our cohort of kidney transplant recipients included 21 (75%) from deceased donors and 7 (25%) from living-related donors. At the time of biopsy, 6 patients (21%) had elevated blood pressure (defined as > 160/90 mm Hg). One patient had severe complications, which included a significant decrease in hemoglobin requiring transfusion and a perinephric hematoma with worsening renal function. This was a morbidly obese patient whose blood pressure was elevated at the time of biopsy with a platelet count of 93 × 10³/mm³ and international normalized ratio of 1.21. CONCLUSIONS: A computed tomography-guided percutaneous kidney transplant biopsy is a safe and effective alternative to obtain kidney tissue in the obese population and is associated with low rates of complications. In this study, we highlighted the need to achieve adequate blood pressure control and assess bleeding risk factors, such as platelet count and international normalized ratio, prior to biopsy.

Hepatic Sarcoidosis: Natural History and Management Implications.

Introduction: Hepatic granulomas are common in patients with sarcoidosis, but clinically significant liver disease is uncommon and poorly studied. We aimed to characterize the frequency and clinical course of hepatic sarcoidosis in an ethnically diverse population. Methods: This is a retrospective study including all cases of hepatic sarcoidosis in a single center. The median follow-up time was 49 months (4-121). Cases were identified based on ICD-9 and ICD-10 codes for granulomatous hepatitis, sarcoidosis, and hepatic sarcoidosis. The Chi-square and Wilcoxon-signed rank tests were used as indicated to assess for differences between groups. Results: Of 286 patients with sarcoidosis, 27 had hepatic involvement; 78% were female and 48% African American. The most common pattern of liver tests abnormalities was cholestatic. Ten patients had clinically significant hepatic involvement: cirrhosis in seven (25.9%), portal hypertension in nine (33%), and portal vein thrombosis in one (3.7%). Sex, race, and ethnicity were not associated with an increased risk of hepatic involvement or symptomatic hepatic sarcoidosis. Most patients received medical treatment, most commonly oral glucocorticoids. At the end of the follow-up period, all patients were alive but two had undergone liver transplantation due to complications of hepatic sarcoidosis. Three patients with hepatic sarcoidosis had initially been classified as AMA-negative PBC. Conclusions: Hepatic sarcoidosis was found in 9.4% of patients with sarcoidosis and was clinically significant in 37% of those. Identifying and monitoring hepatic sarcoidosis is crucial given its potential complications.

Update in the Care and Management of Patients with Primary Sclerosing Cholangitis.

PURPOSE OF REVIEW: Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease for which specific medical therapy is not available. The goals of treatment are primarily early detection and management of complications. In this review, we discuss novel therapies under evaluation and provide the foundation for surveillance strategies. RECENT FINDINGS: Drugs under investigation include norursodeoxycholic acid, nuclear receptor agonists, anti-fibrotics, antibiotics, and anti-inflammatory drugs. Endoscopic therapy is indicated for symptomatic dominant strictures and in the work-up of malignancies. Recently, the use of stents was associated with an increased rate of complications compared to balloon dilatation; and long-term stenting should be avoided. Malignancies currently account for most of the PSC-related mortality. Many drugs are emerging for the treatment of PSC but liver transplantation is the only treatment modality shown to prolong survival. PSC recurrence occurs in up to 35% of transplanted allografts within a median of 5 years. Surveillance for hepatobiliary and colorectal malignancies is indicated.

Treatment patterns, testicular loss and disparities in inpatient surgical management of testicular torsion in boys: a population-based study 1998-2010.

OBJECTIVES: To examine temporal trends in inpatient testicular torsion (TT) treatment and testicular loss (TL), and to identify risk factors for TL using a large nationally representative paediatric cohort, stratified to established high prevalence TT cohorts (neonatal TT [NTT]; age <1 years) and adolescent TT (ATT; age 12-17 years). METHODS: Boys (age ≤17 years, n = 17 478) undergoing surgical exploration for TT were identified within the Nationwide Inpatient Sample (1998-2010). Temporal trends in inpatient TT management (salvage surgery vs orchiectomy) and TL were examined using estimated annual percent change methodology. Multivariable logistic regression models were used to identify risk factors for TL. RESULTS: Teaching hospitals treated 90% of boys with NTT, compared with 55% with ATT (P < 0.001). Of boys with NTT, 85% lost their testis, compared with 35% with ATT (P < 0.001). Inpatient management of NTT declined during the study period, from 7.5/100 000 children in 1998 to 3/100 000 in 2010 (estimated annual percent change -4.95%; P < 0.001). The decrease was similar but less dramatic in ATT. TL patterns did not improve. In adjusted analyses, for NTT, orchiectomy was more likely at teaching hospitals. For ATT, orchiectomy was more likely in children with comorbidities (odds ratio 5.42; P = 0.045), Medicaid coverage or self-pay (P < 0.05) and weekday presentation (P = 0.001). Regional or racial disposition was not associated with TL. CONCLUSIONS: There has been a gradual decrease in inpatient surgical treatment for both NTT and ATT, presumably as a result of increased outpatient and/or non-operative management of these children. Concerningly, TL patterns have not improved; targeted interventions such as parental and adolescent male health education may lead to timely recognition/intervention in children at-risk for ATT. We noted no regional/racial disparities in contrast to earlier studies.

Enhancement and validation of an Arab surname database.

OBJECTIVES: Arab Americans constitute a large, heterogeneous, and quickly growing subpopulation in the United States. Health statistics for this group are difficult to find because US governmental offices do not recognize Arab as separate from white. The development and validation of an Arab- and Chaldean-American name database will enhance research efforts in this population subgroup. METHODS: A previously validated name database was supplemented with newly identified names gathered primarily from vital statistic records and then evaluated using a multistep process. This process included 1) review by 4 Arabic- and Chaldean-speaking reviewers, 2) ethnicity assessment by social media searches, and 3) self-report of ancestry obtained from a telephone survey. RESULTS: Our Arab- and Chaldean-American name algorithm has a positive predictive value of 91 percent and a negative predictive value of 100 percent. CONCLUSIONS: This enhanced name database and algorithm can be used to identify Arab Americans in health statistics data, such as cancer and hospital registries, where they are often coded as white, to determine the extent of health disparities in this population.