Early neurologic complications after liver transplant are associated with reduced long-term survival and increased rates of rejection.

Neurologic complications (NCs) are common following liver transplantation (LT) and have been associated with impaired short-term survival. The impact of NC on long-term survival is less defined. We aimed to characterize these outcomes and assess for risk factors for post-LT NC. We performed a single-center, retrospective review of 521 patients with LT from 2016 to 2020. Baseline clinical and laboratory factors, intraoperative events, and outcomes were compared between patients with and without NC. The 5-year overall and rejection-free survival was estimated using the Kaplan-Meier analysis. Multivariable logistic regression assessed for an independent relationship between risk factors and the development of NC. Among 521 LT recipients, 24% experienced post-LT NC. Overall and rejection-free survival at 5 years was, respectively, 69% and 75% among those with NC versus 87% and 88% among those without NC (log-rank < 0.001). Among those who survived the first 3 months after LT, overall survival but not rejection-free survival was reduced among patients with NC. Risk factors for developing NC included peri-LT serum sodium (ΔSNa) ≥ 6 (29.4% vs. 20.5%, p = 0.04), grade 3 or 4 HE pre-LT, SNa < 125 pre-LT, and more intraoperative transfusions. In a multivariable logistic regression model controlling for described variables, SNa < 125 (or 0.21, 95% CI, 0.06-0.74) at LT and pre-LT HE grade 3 or 4 (or 0.45, 95% CI, 0.26-0.76) was independently associated with NC. Long-term survival was reduced among patients who developed NC in the immediate post-transplant period, even when censoring those who died in the first 3 months. Post-LT NC was associated with perioperative ΔSNa ≥ 6. Optimization of SNa pre-LT > 125 and limiting perioperative ΔSNa <6 mEq/L might have a beneficial impact in decreasing NC post-LT, which may improve long-term post-LT survival.

Long-term outcomes after liver transplantation in the Hispanic population.

BACKGROUND & AIMS: Racial/ethnic disparities in liver transplantation (LT) are well-recognized. Although Hispanics represent the largest and youngest minority group in the United States, limited data exist on long-term outcomes. We aimed to investigate long-term post-liver transplant outcomes in Hispanic patients and identify potential disparities compared to a baseline demographic of non-Hispanic white patients. METHODS: We performed a retrospective cohort study of first-time liver transplant recipients using the United Network for Organ Sharing database from 2002 to 2013, with follow-up through 2018. The primary outcomes of interest were overall patient and graft survival after LT. RESULTS: 45 767 patients underwent LT (85.0% non-Hispanic white, 15.0% Hispanic). Hispanics had lower socioeconomic status, higher prevalence of pretransplant comorbidities and more severe liver disease compared to non-Hispanic whites. Hispanics had similar patient (76.6% vs 75.6%; P = .12) and graft (71.7% vs 70.8%; P = .28) survival at 5 years and significantly better patient (62.9% vs 59.7%; P < .001) and graft (58.6% vs 55.6%; P = .002) survival at 10 years. In multivariable analysis, Hispanics had lower associated all-cause mortality (HR 0.86, 95% CI, 0.82-0.91; P < .001) and graft failure (HR 0.89, 95% CI, 0.85-0.93; P < .001) compared to non-Hispanic whites. In etiology-specific subanalysis, Hispanics transplanted for ALD, NASH and HCV had lower all-cause mortality compared to non-Hispanic whites. CONCLUSIONS: Hispanics have similar or better long-term post-LT outcomes compared to non-Hispanic whites despite a worse pretransplant risk factor profile. Further research is needed to clarify if this survival advantage reflects uncaptured protective factors or more stringent transplant selection in the Hispanic population.

The Pharmacologic Management of Osteoporosis in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Osteoporosis is a common complication of primary biliary cholangitis (PBC) yet evidence for effective therapy is lacking. We sought to review all randomized controlled trials evaluating pharmacotherapy against placebo or no intervention for treatment of osteoporosis in PBC. METHODOLOGY: A comprehensive database search was conducted from inception through 29 March 2017. The primary outcome was incidence of fractures; secondary outcomes were change in bone mineral density (BMD) and adverse events. We assessed studies for risk of bias, graded quality of evidence, and used meta-analysis to obtain overall effect by pooling studies of the same drug class. RESULTS: We identified 11 randomized controlled trials evaluating bisphosphonates (3), hormone replacement therapy (2), ursodeoxycholic acid (1), obeticholic acid (1), cyclosporin A (1), vitamin K (1), calcitriol (1), and sodium fluoride (1). No intervention significantly reduced fractures compared to control. Although significant improvement in BMD was seen in one study with alendronate, a third-generation bisphosphonate, no significant improvement was seen on pooled analysis of all bisphosphonates including first-generation bisphosphonates (standard mean difference 0.41, p = 0.68). On pooled analysis, hormone replacement therapy modestly improved lumbar BMD (standard mean difference 0.69, p = 0.02), but with significantly increased adverse events (odds ratio 8.82, p = 0.01). CONCLUSIONS: There is a lack of high-quality evidence supporting the efficacy of any treatment of osteoporosis in PBC. This may be explained by lack of power in the included studies. However, our current understanding of PBC-related osteoporosis indicates that it results from decreased bone formation, which may explain the attenuated effect of traditional antiresorptive agents. Future studies should investigate newer anabolic bone agents.

Association Between Endoscopist Personality and Rate of Adenoma Detection.

BACKGROUND & AIMS: There is significant variation among endoscopists in their adenoma detection rates (ADRs). We explored associations between ADR and characteristics of endoscopists, including personality traits and financial incentives. METHODS: We collected electronic health record data from October 2013 through September 2015 and calculated ADRs for physicians from 4 health systems. ADRs were risk-adjusted for differences in patient populations. Physicians were surveyed to assess financial motivations, knowledge and perceptions about colonoscopy quality, and personality traits. Of 140 physicians sent the survey, 117 responded. RESULTS: The median risk-adjusted ADR for all surveyed physicians was 29.3% (interquartile range, 24.1%-35.5%). We found no significant association between ADR and financial incentives, malpractice concerns, or physicians' perceptions of ADR as a quality metric. ADR was associated with the degree of self-reported compulsiveness relative to peers: among endoscopists who described themselves as much more compulsive, the ADR was 33.1%; among those who described themselves as somewhat more compulsive, the ADR was 32.9%; among those who described themselves as about the same as others, the ADR was 26.4%; and among those who described themselves as somewhat less compulsive, the ADR was 27.3%) (P = .0019). ADR was also associated with perceived thoroughness (much more thorough than peers, ADR = 31.5%; somewhat more, 31.9%; same/somewhat less, 27.1%; P = .0173). Physicians who reported feeling rushed, having difficulty pacing themselves, or having difficulty in accomplishing goals had higher ADRs. A secondary analysis found the same associations between personality and adenomas per colonoscopy. CONCLUSIONS: We found no significant association between ADR and financial incentives, malpractice concerns, or perceptions of ADR as a quality metric. However, ADRs were higher among physicians who described themselves as more compulsive or thorough, and among those who reported feeling rushed or having difficulty accomplishing goals.

Hospital-level balloon tamponade use is associated with increased mortality for all patients presenting with acute variceal haemorrhage.

BACKGROUND & AIMS: Balloon tamponade (BT) can bridge patients to salvage therapy for uncontrollable acute variceal haemorrhage (AVH). However, data are limited regarding the reasons for, rate of and outcomes associated with Balloon tamponade use. METHODS: First, we performed an single-centre cohort study of all patients (N = 139) with oesophageal acute variceal haemorrhage from 01/2009 to 10/2015. Associations between Balloon tamponade use and adherence to four quality metrics (endoscopy within 12 hours, band-ligation, pre-endoscopy antibiotics and octreotide) were evaluated. Second, we analysed the National Inpatient Sample (2005-2011) to determine the association between in-hospital mortality for patients and their hospital's Balloon tamponade-utilization to acute variceal haemorrhage volume ratio. RESULTS: In the national cohort, 5.5% of 140 521 acute variceal haemorrhage admissions required Balloon tamponade utilization. Adjusting for patient- and hospital-level confounders, the rate of Balloon tamponade use per acute variceal haemorrhage managed at any given hospital was associated with increased mortality for all-comers with acute variceal haemorrhage. Compared to the lowest tertile, acute variceal haemorrhage admissions in the highest Balloon tamponade utilizers were associated with increased mortality of (OR1.17 95%CI (1.01-1.37). In the single-centre cohort, 14 (10.1%) patients required Balloon tamponade. Balloon tamponade utilization was significantly associated with alcohol abuse (50.4% vs 21.4%, P = .04), hepatocellular carcinoma (35.7% vs 8.8%, P = .01), higher median model for end-stage liver disease (MELD) score (26.3vs15.5, P = .002) and active bleeding during endoscopy (64.3% vs 27.5%, P = .01). Failure to provide all quality metrics was associated with a higher model for end-stage liver disease-adjusted risk of Balloon tamponade use: OR 16.7 95% CI(4.17-100.0, P < .0001). CONCLUSION: Balloon tamponade use is associated with severity of bleeding but may also implicate deficits in processes of care. Even for patients who did not need Balloon tamponade, presentation to hospitals with high Balloon tamponade utilization increases their odds of dying from acute variceal haemorrhage.

A National Survey of the Prevalence and Impact of Cytomegalovirus Infection Among Hospitalized Patients With Ulcerative Colitis.

GOALS: To estimate the effect of cytomegalovirus (CMV) in patients with ulcerative colitis (UC), and compare these outcomes to patients with CMV without UC. BACKGROUND: The impact of CMV infection in UC is not well understood. STUDY: We analyzed records from the Nationwide Inpatient Sample (NIS) of patients with UC and CMV between 2006 and 2012. Differences in outcomes were determined between patients with UC and CMV and those with UC without CMV. Secondary analysis compared outcomes of patients with UC and CMV to patients with CMV alone. RESULTS: Patients with UC and CMV (n=145) had longer length of stay (16.31 vs. 5.52 d, P<0.0001), higher total charges ($111,835.50 vs. $39.895, P=0.001), and were less likely to be discharged home without services (50.0% vs. 81.83%, P<0.0001) compared with patients with UC without CMV (n=32,290). On regression analysis, CMV was significantly associated with higher total charges (P<0.01) and longer length of stay (P<0.01), but not for increased need for colorectal surgery. When comparing patients with UC and CMV to patients with CMV alone (n=14,960), patients with CMV alone had a higher Charlson Comorbidity Index and a trend toward higher in-hospital mortality. CONCLUSIONS: CMV infection in hospitalized patients with UC is associated with a longer length of stay, increased total charges, and fewer routine discharges, but not increased surgery or mortality. Patients with CMV alone had the worst outcomes of all groups suggesting that CMV in UC patients may not have the same negative impact as in other diseases.

The utility and complications of plasma administration in cirrhotic patients undergoing minimally invasive procedures.

Patients with cirrhosis have coagulopathy often necessitating correction with blood products, such as plasma products (fresh frozen plasma and plasma frozen within 24 h) prior to certain invasive procedures. However, plasma administration has the potential for substantial negative adverse effects such as volume overload, transfusion-related lung injury and allergic/anaphylactic reactions. In addition, its effectiveness in preventing bleeding is similarly unclear. The purpose of this study was to determine the safety and efficacy of plasma administration in cirrhotic patients undergoing minimally invasive procedures, specifically vascular access placement, transjugular liver biopsies, renal biopsies and thoracenteses. In this retrospective cohort study, we identified patients receiving plasma products in preparation for an invasive procedure, with the primary outcomes of volume overload and bleeding. Of the 145 transfusion events that met the criteria from 2015 to 2018, the median INR decreased from 2.7 to 2.2 pre and post plasma administration and 13.8% of recipients had complications of volume overload. The cost of acquisition of plasma administered below clinically impactful doses accumulates to an estimated 19 000 dollars over this time period, not including nursing preparation or production costs. Plasma products minimally, if at all, improved laboratory values of coagulation and in some patients led to adverse effects.

Donor Characteristics and Regional Differences in the Utilization of HCV-Positive Donors in Liver Transplantation.

Importance: Increased utilization of hepatitis C virus (HCV)-positive liver allografts for liver transplant (LT) has been endorsed as one of several ways to combat national organ shortages. However, HCV-positive donors remain poorly characterized, and Organ Procurement and Transplantation Network regional differences in the utilization of HCV-positive liver allografts are unclear. Objective: To characterize HCV-positive donors and the allografts that come from them. Design, Setting, and Participants: In this cross-sectional study, the Scientific Registry of Transplant Recipients database was queried for all donors who underwent HCV testing from June 2015 to December 2018. Clinical and allograft characteristics were evaluated, and utilization across the United States was studied. Patients with positive or negative results for HCV antibody (Ab) and HCV nucleic acid amplification testing (NAT) were included in this study. Donors utilized for living donor transplant and pediatric (age <18 years) recipients were excluded. Main Outcomes and Measures: The primary comparison was between donors who were HCV Ab positive and those who were HCV Ab negative. Regional variations in the utilization of HCV-positive and HCV-negative donors were analyzed. Results: Of 24 500 donors utilized for LT, 1887 (7.7%) were HCV Ab positive; 64.4% of HCV Ab-positive donors were HCV NAT positive. HCV Ab-positive donors were younger (median [interquartile range] age, 35 [29-46] years vs 40 [27-54] years) and had fewer comorbidities, such as diabetes (8.3% vs 12.0%) and hypertension (25.9% vs 35.2%), compared with HCV Ab-negative donors. These findings were even more pronounced in HCV Ab-positive /NAT-positive compared with HCV Ab-positive/NAT-negative donors. Organ Procurement and Transplantation Network regions 2, 3, 10, and 11 had the highest absolute utilization of HCV Ab-positive donors, accounting for 64.4% of all HCV Ab-positive donors used in the United States. Region 1 had the highest relative utilization of HCV Ab-positive donors (18.7%). The use of HCV Ab-positive donors in some regions was associated with the rate of drug overdose, but this was not always the case. Similar utilization results were found with HCV NAT-positive donors. Conclusions and Relevance: In this cross-sectional study, HCV-positive donors were younger and healthier than utilized HCV-negative donors. Significant differences exist in the utilization of HCV-positive donors across the 11 Organ Procurement and Transplantation Network regions, which is not entirely explained by organ demand or by higher availability of HCV-positive livers as per the distribution of the opioid epidemic. Initiatives to increase the use of HCV-positive donors, particularly in regions of high organ demand, should be implemented.

Differential Associations of Circulating MicroRNAs With Pathogenic Factors in NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous disease driven by genetic and environmental factors. MicroRNAs (miRNAs) serve as pleiotropic post-transcriptional regulators of cellular pathways. Although several miRNAs have been associated with NAFLD and fibrosis, there are limited studies in humans examining their differential association with pathogenic factors or histological features of NAFLD. We examined the differential relationships of five of the best-described circulating microRNAs (miR-34a, miR-122, miR-191, miR-192, and miR-200a) with histological features and pathogenic factors of NAFLD. A cross-sectional study was conducted to examine the relationship between relative levels of circulating microRNAs standardized by z-scores and histological features of NAFLD, common NAFLD genetic polymorphisms, and insulin resistance measured by the enhanced lipoprotein insulin resistance index in 132 subjects with biopsy-proven NAFLD. We found that miR-34a, miR-122, miR-192, miR-200a, but not miR-191, strongly correlate with fibrosis in NAFLD by increases of 0.20 to 0.40 SD (P < 0.005) with each stage of fibrosis. In multivariate analysis, miR-34a, miR-122, and miR-192 levels are independently associated with hepatic steatosis and fibrosis, but not lobular inflammation or ballooning degeneration, whereas miR-200a is only associated with fibrosis. Among the four miRNAs, miR-34a, miR-122, and miR-192 are associated with pathogenic factors of NAFLD, including insulin resistance measured by eLP-IR, patatin-like phospholipase domain containing 3 I148M, and transmembrane 6 superfamily 2 (TM6SF2) E167K polymorphisms. In contrast, miR-200a is only associated with the TM6SF2 E167K variant. Finally, miR-34a has the strongest predictive value for various stages of fibrosis, with C-statistic approximates-combined predictive score for miRNAs. Conclusion: miR-34a, miR-122, miR-192, and miR-200a demonstrate strong associations with NAFLD severity by histology, but differential associations with pathogenic factors.

Increased Morbidity and Mortality Associated with Falls Among Patients with Cirrhosis.

BACKGROUND: Injuries are more morbid and complicated to manage in patients with cirrhosis. However, data are limited regarding the relative risk of injury and severity of injury from falls in patients with cirrhosis compared with those without cirrhosis. METHODS: We examined the nationally representative National Emergency Department Sample, an all-payer database including all patients presenting with falls, 2009-2012. We determined the relative risks for and clinical associations with severe injuries. Outcomes included hospitalization, length of stay, costs, and in-hospital death. Outcomes were compared with those of patients with congestive heart failure. RESULTS: We identified 102,977 visits involving patients with cirrhosis and 26,996,120 involving patients without cirrhosis who presented with a fall. Overall and compared with patients with congestive heart failure, the adjusted risk of severe injury was higher for patients with cirrhosis. These included intracranial hemorrhage (2.33; 95% confidence interval [CI], 2.02-2.68), skull fracture (1.75; 95% CI, 1.53-2.00), and pelvic fracture (1.71; 95% CI, 1.56-1.88). Risk was lower for less-severe injuries, such as concussion (0.95; 95% CI, 0.86-1.06) and lower-leg fracture (0.86; 95% CI, 0.80-0.91). Risk factors significantly positively associated with severe injury on multivariate analysis were hepatic encephalopathy, alcohol abuse, and infection. Cirrhosis was associated with increased risk of in-hospital death, longer length of stay, and higher costs after a fall. All outcomes were worse compared with those for patients with congestive heart failure CONCLUSION: Falls are common in patients with cirrhosis, and they are more likely to incur severe injuries, with increased hospital costs and risk of death. Poor outcomes are most associated with ascites, hepatic encephalopathy, alcohol abuse, and infection, highlighting the subgroups at highest risk and most likely to benefit from preventative interventions.

Extra-pancreatic complications, especially hemodialysis predict mortality and length of stay, in ICU patients admitted with acute pancreatitis.

BACKGROUND AND AIMS: Patients in the intensive care unit (ICU) with acute pancreatitis (AP) are at risk for extra-pancreatic complications given their severe illness and prolonged length of stay. We sought to determine the rate of extra-pancreatic complications and its effect on length of stay (LOS) and mortality in ICU patients with AP. METHODS: We performed a retrospective cohort study of ICU patients admitted to a tertiary-care center with a diagnosis of AP. A total of 287 ICU patients had a discharge diagnosis of AP, of which 163 met inclusion criteria. We calculated incidence rates of extra-pancreatic complications and performed a univariate and multi-variable analysis to determine predictors of LOS and mortality. RESULTS: There were a total of 158 extra-pancreatic complications (0.97 extra-pancreatic complications per patient). Ninety-five patients had at least one extra-pancreatic complication, whereas 68 patients had no extra-pancreatic complications. Patients with extra-pancreatic complications had a significantly longer LOS (14.7 vs 8.8 days, p < 0.01) when controlling for local pancreatic complications. Patients with non-infectious extra-pancreatic complications had a higher rate of mortality (24.0% vs 16.2%, p = 0.04). Patients requiring dialysis was an independent predictor for LOS and mortality (incidence risk ratio [IRR] 1.73, 95% confidence interval [CI]: 1.263-2.378 and IRR 1.50, 95% CI 1.623-6.843, p < 0.01) on multi-variable analysis. Coronary events were also a predictor for mortality (p = 0.05). Other extra-pancreatic complications were not significant. CONCLUSIONS: Extra-pancreatic complications occur frequently in ICU patients with AP and impact LOS. Patients with non-infectious extra-pancreatic complications have a higher mortality rate. After controlling for local pancreatic complications, patients requiring dialysis remained an independent predictor for LOS and mortality.

Risk prediction model for heart failure and cardiomyopathy after adjuvant trastuzumab therapy for breast cancer.

BACKGROUND: Adjuvant trastuzumab improves survival for women with human epidermal growth factor receptor 2-positive breast cancer, but increases risk for heart failure (HF) and cardiomyopathy (CM). However, clinical trials may underestimate HF/CM risk because they enroll younger subjects with fewer cardiac risk factors. We sought to develop a clinical risk score that identifies older women with breast cancer who are at higher risk of HF or CM after trastuzumab. METHODS AND RESULTS: Using the Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified women with breast cancer who received adjuvant trastuzumab. Using a split-sample design, we used a proportional hazards model to identify candidate predictors of HF/CM in a derivation cohort. A risk score was constructed using regression coefficients, and HF/CM rates were calculated in the validation cohort. The sample consisted of 1664 older women (mean age 73.6 years) with 3-year HF/CM rate of 19.1%. A risk score consisting of age, adjuvant chemotherapy, coronary artery disease, atrial fibrillation or flutter, diabetes mellitus, hypertension, and renal failure was able to classify HF/CM risk into low (0 to 3 points), medium (4 to 5 points), and high (≥6 points) risk strata with 3-year rates of 16.2%, 26.0%, and 39.5%, respectively. CONCLUSIONS: A 7-factor risk score was able to stratify 3-year risk of HF/CM after trastuzumab between the lowest and highest risk groups by more than 2-fold in a Medicare population. These findings will inform future research aimed at further developing a clinical risk score for HF/CM for breast cancer patients of all ages.