The incidence of adverse outcome in donors after living donor liver transplantation: A meta-analysis of 60,829 donors.

The scarcity of liver grafts has prompted developments in living donor liver transplantations (LDLT), with previous literature illustrating similar outcomes in recipients compared to deceased donor transplants. However, significant concerns regarding living donor morbidity and mortality have yet to be examined comprehensively. This study aims to provide estimates of the incidence of various outcomes in living liver donors. In this meta-analysis, Medline and Embase were searched from inception to July 2022 for articles assessing the incidence of outcomes in LDLT donors. Complications in the included studies were classified into respective organ systems. Analysis of incidence was conducted using a generalized linear mixed model with Clopper-Pearson intervals. Eighty-seven articles involving 60,829 living liver donors were included. The overall pooled incidence of complications in LDLT donors was 24.7% (CI: 21.6%-28.1%). The incidence of minor complications was 17.3% (CI: 14.7%-20.3%), while the incidence of major complications was lower at 5.5% (CI: 4.5%-6.7%). The overall incidence of donor mortality was 0.06% (CI: 0.0%-0.1%) in 49,027 individuals. Psychological complications (7.6%, CI: 4.9%-11.5%) were the most common among LDLT donors, followed by wound-related (5.2%, CI: 4.4%-6.2%) and respiratory complications (4.9%, CI: 3.8%-6.3%). Conversely, cardiovascular complications had the lowest incidence among the subgroups at 0.8% (CI: 0.4%-1.3%). This study presents the incidence of post-LDLT outcomes in living liver donors, illustrating significant psychological, wound-related, and respiratory complications. While significant advancements in recent decades have contributed towards decreased morbidity in living donors, our findings call for targeted measures and continued efforts to ensure the safety and quality of life of liver donors post-LDLT.

Transplanting hepatitis B surface antigen-positive livers in the United States: Outcomes and opportunities.

Livers from donors with positive hepatitis B surface antigens (HBsAg+) have been used to expand the donor pool; however, outcome data are limited. We aim to evaluate survival following liver transplant (LT) from HBsAg+ donors. Using the United Network for Organ Sharing registry, we identified HBsAg+ donors used for LT from 2009 to 2020. We used Kaplan-Meier survival and Cox proportional hazards regression to compare post-LT survival in hepatitis B virus-negative recipients who utilized HBsAg+ donors to propensity-matched cohorts who utilized other types of donors. From 2009-2020, 70 patients received HBsAg+ livers, and 58 of them did not carry a diagnosis of chronic hepatitis B virus. The 1- and 3-year post-LT survival for hepatitis B virus-negative patients who received livers from HBsAg+ donors were 96.6% and 91.4%, respectively, with no statistical differences compared with patients who received livers from hepatitis C virus viremic donors (96.5%/93.0%, P = .961/.427), donation after cardiac death donors (93.0%/86.0%, P = .651/.598), average-risk donors (89.5%/86.0%, P = 0.264/0.617), and a combination of extended-criteria donors, including donation after cardiac death, donor age over 70, and graft with greater than 30% steatosis (93.0%/91.2%, P = .621/.785). Recipients of HBsAg+ livers have similar post-LT survival compared with those receiving other types of grafts. Increasing the utilization of HBsAg+ livers could safely expand the donor pool.

Long-term outcomes and trends in liver transplantation for hereditary hemochromatosis in the United States.

There have been conflicting data regarding liver transplantation (LT) outcomes for hereditary hemochromatosis (HH), with no recent data on LT outcomes in patients with HH in the past decade. Using the United Network for Organ Sharing registry, we evaluated waitlist and post-LT survival in all adult patients listed for HH without concomitant liver disease from 2003 to 2019. Post-LT survival for HH was compared with a propensity-matched (recipient and donor factors) cohort of recipients with chronic liver disease (CLD). From 2003 to 2019, 862 patients with HH were listed for LT, of which 55.6% ( n = 479) patients underwent LT. The 1- and 5-year post-LT survival rates in patients with HH were 88.7% (95% confidence interval [CI], 85.4%-91.4%) and 77.5% (95% CI, 72.8%-81.4%), respectively, and were comparable with those in the propensity-matched CLD cohort ( p value = 0.96). Post-LT survival for HH was lower than for Wilson's disease, another hereditary metabolic liver disease with similar LT volume ( n = 365). Predictors for long-term (5-year) post-LT mortality included presence of portal vein thrombosis (hazard ratio [HR], 1.96; 95% CI, 1.07-3.58), obesity measurements greater than Class II (HR, 1.98; 95% CI, 1.16-3.39), and Karnofsky performance status (HR, 0.98; 95% CI, 0.97-0.99) at the time of LT. The leading cause of post-LT death ( n = 145) was malignancy (25.5%), whereas cardiac disease was the cause in less than 10% of recipients. In conclusion, short- and long-term survival rates for HH are excellent and comparable with those of other LT recipients. Improving extrahepatic metabolic factors and functional status in patients with HH prior to LT may improve outcomes.

Optimal alpha-1 antitrypsin level cutoffs for genotype identification in patients with chronic liver disease.

BACKGROUND: Controversy exists whether alpha-1 antitrypsin (A1AT) genotype testing should be performed as a first-line screening for A1AT heterozygous variants. METHODS: We calculated the median and interquartile range of A1AT level for each genotype in 4378 patients with chronic liver disease and "miss rate" of MZ genotype identification at various cutoff levels. FINDINGS: Significant overlap in A1AT level noted with Pi*MM, MZ, and MS variants. Miss rate of Pi*MZ at a cutoff level <100 was 29%, <110 was 18%, <120 was 8%, and <130 was 4%. We suggest simultaneous measurement of A1AT level and genotype in patients with chronic liver disease.

Alpha-1-Antitrypsin Pi*MZ variant increases risk of developing hepatic events in nonalcoholic fatty liver disease patients.

AIMS: Heterozygous alpha-1-antitrypsin (A1AT) Pi*MZ variant has been shown to increase the risk of developing liver cirrhosis in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to determine the association between heterozygous Pi*MZ and Pi*MS variants and development of hepatic decompensation events in NAFLD patients. METHODS: We included patients with NAFLD who also had A1AT genotyping performed from 2005 to 2020. We recorded demographic and clinical variables, and data on hepatic events (ascites, hepatic encephalopathy, esophageal variceal bleed, or hepatocellular carcinoma), if any. We performed binary logistic regression analysis to assess the association between A1AT variants and hepatic events, and calculated Odds ratio (OR) with their 95% confidence intervals (Cl). RESULTS: We included 1532 patients with NAFLD, of which 1249 patients had Pi*MM, 121 had Pi*MS, and 162 had Pi*MZ. Of the 1532 patients, hepatic events developed in 521 (34%) patients. The percentage of patients with Pi*MZ variant was significantly higher in patients with hepatic events as compared to patients without hepatic events (18.7 % vs 8.1%, p<0.0001). Pi*MZ variant was noted to significantly increase the odds of developing hepatic events in NAFLD patients, unadjusted OR: 1.82 (1.3-2.5, p<0.001), adjusted OR (for age, sex, body mass index, and diabetes mellitus) 1.76 (1.2-2.5, p = 0.002). Pi*MS variant did not increase the odds of hepatic events in NAFLD patients, OR: 0.92 (0.6-1.4, p = 0.70). CONCLUSION: Patients with NAFLD and A1AT Pi*MZ variant are at increased risk for developing hepatic decompensation. NAFLD patients should be offered A1AT genotyping for risk stratification, counseling, and multidisciplinary intervention for NAFLD.

Chilaiditi Syndrome: A Case Report, Literature Review, and Proposition of a Novel Management Staging System.

Chilaiditi's sign refers to colonic interposition between the liver and the diaphragm in the right subphrenic space secondary to the relaxation of the suspensory ligaments of the right colic flexure. The diagnosis of Chilaiditi's sign is based on radiological findings with the following three criteria: 1) The right hemidiaphragm must be adequately elevated above the liver by the intestine, 2) the bowel must be distended by air to illustrate pseudo-pneumoperitoneum, and 3) the superior margin of the liver must be depressed below the level of the left hemidiaphragm. In this report, we present the case of a 49-year-old female presenting with signs and symptoms suggestive of Chilaiditi syndrome managed with laparoscopic surgery. We also present a literature review with a summary of previous studies and propose a novel management staging system for this syndrome.

Laparoscopic Repair of Small Bowel Obstruction Caused by an Intersigmoid Hernia: A Case Report.

Bowel obstructions can be caused by internal hernias which are protrusions of the bowel into openings within the abdominal cavity. There are various types of internal hernias including sigmoid hernias which involve the sigmoid mesentery.Sigmoid hernias are very difficult to diagnose clinically, even with the aid of radiologic imaging. Computed tomography (CT) scan findings often reveal small bowel obstructions; however, they are not sensitive to intersigmoid hernias. Most of these rare herniations are repaired by open abdominal surgery followed by the closure of the mesenteric defect to prevent a recurrence. We present the case of a 57-year-old man who presented to the emergency department with a small bowel obstruction that was caused by an intersigmoid hernia and was successfully repaired through a minimally invasive laparoscopic approach. This case demonstrates an intra-operative diagnosis of an intersigmoid hernia and reviews the benefits of a laparoscopic approach for the reduction of the sigmoid mesentery.

Increasing Fecal Immunochemical Test Return Rates by Implementing Effective "Reminder to Complete Kit" Communication With Participants: A Quality Improvement Study.

Background The incidence of colorectal cancer (CRC) in the United States is increasing. It remains the second leading cause of cancer death in the United States for men and women combined, mainly due to underutilization of screening methods. The American Cancer Society now recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high-sensitivity stool-based test or structural (visual) examination, depending on patient preference and test availability. The primary objective of this quality improvement project was to determine if reminder methods, such as telephone or letter reminders, increased the return rate of fecal immunochemical tests (FIT) for CRC screening. Methodology At public outreach events and daily clinics in the West Texas Panhandle area, participants in the GET FIT program were provided with FIT kits after completing the education on CRC. Participants who fit the inclusion criteria and had received a FIT kit from the program were included. They were instructed on how to perform the test and mail it back. Participants who did not return the completed kits within two weeks were reminded either through (1) a reminder letter, (2) telephone, or (3) a combination of letter reminder and telephone call every two weeks (±three days) for 60 days or five attempts to contact. We de-identified and analyzed the FIT kit return data from April-September 2019 before analyzing these reminder methods. We then calculated the change in return rates from October 2019 to March 2020. Our goal was to increase the FIT return rates by 25% compared to the baseline return rate. Results The pre-intervention return rate of kits for April-September 2019 was 61.52%, and the post-intervention return rate for October 2019-March 2020 was 71.85%. This rate was equal to an approximately 16.79% increase in return rates that was statistically significant (p < 0.01). There was a significant difference in the method of reminder between the two groups, but no significant differences in gender and race/ethnicity between the two groups. There was a significant difference in return rates between race/ethnicities in the October-March cohort with black and Hispanic participants having the highest return rates of 82.3% and 77.25%, respectively. Conclusions FIT remains one of the primary options for CRC screening. Due to its lower cost and noninvasiveness, FIT was offered to patients at average risk. We demonstrated an increase in return rates, although we did not meet our target return rate goal for this project. This study was limited due to a gradual increase in coronavirus disease 2019 (COVID-19) cases and a subsequent shift and conversation of ongoing research into COVID-19.

Hepatic Manifestations of Nonhepatotropic Infectious Agents Including Severe Acute Respiratory Syndrome Coronavirus-2, Adenovirus, Herpes Simplex Virus, and Coxiella burnetii.

Nonhepatotropic viruses such as adenovirus, herpes simplex virus, flaviviruses, filoviruses, and human herpes virus, and bacteria such as Coxiella burnetii, can cause liver injury mimicking acute hepatitis. Most of these organisms cause a self-limited infection. However, in immunocompromised patients, they can cause severe hepatitis or in some cases fulminant hepatic failure requiring an urgent liver transplant. Hepatic dysfunction is also commonly seen in patients with severe acute respiratory syndrome coronavirus-2 infection. Patients with preexisting liver diseases are likely at risk for severe coronavirus disease 2019 (COVID-19) and may be associated with poor outcomes.

Probabilistic Modeling Approach to Reducing Healthcare Costs With Reflex Testing.

OBJECTIVE: Statistical methods can be utilized to optimize the order for reflex diagnostic testing to attenuate patient and hospital costs without affecting quality of care. Our objective is to demonstrate the method of developing an order for testing and to apply this method to an illustrative example. METHODS: An algorithm was developed for minimizing costs for any given number of diagnostic tests, and it was retrospectively applied to a sample. RESULTS: The actual scenario of using both tests on all patients was compared to 2 other hypothetical reflex testing approaches: all patients are given 1 test, and those patients who tested negative were then given the second test. The 2 scenarios would have saved 37.1% and 17.4% in testing costs, respectively. CONCLUSION: These calculations could be applied to numerous situations to reduce costs for patients and hospitals. We propose that this methodology would be best used in conjunction with any existing quality improvement initiatives.

Dyslipidemia, weight gain, and decreased growth velocity in a 14-year-old male.

A 14-year-old male was referred for dyslipidemia. His findings were consistent with metabolic syndrome. Although he lacked the typical physical appearance, his accelerated weight gain combined with a decreased linear growth velocity suggested Cushing syndrome. He was subsequently found to have adrenocorticotropic hormone-independent Cushing syndrome secondary to primary pigmented nodular adrenal disease without Carney Complex. After bilateral adrenalectomy, his lipid profile returned to normal. In this article, we discuss the role of glucocorticoids on lipid and lipoprotein metabolism.

Novel association of polymorphic genetic variants with predictors of outcome of catheter ablation in atrial fibrillation: new directions from a prospective study (DECAF).

PURPOSE: Non-pulmonary vein (non-PV) triggers and left atrial (LA) scars perpetuate atrial fibrillation (AF) and limit the success rate of catheter ablation. In order to understand the genetic basis of these risk factors, we examined the association of selected single nucleotide polymorphisms (SNPs) with scar and non-PV triggers. METHODS: Four hundred AF patients (67 %male, 62±12 years, LA size 45.3±7 mm, 64%non-paroxysmal) undergoing catheter ablation were prospectively enrolled. DNA extractions for16 AF-related SNPS from blood samples were performed of which 371 DNA samples were available for genotyping. Multivariate logistic regression analysis was used for assessing predictive role of individual SNP, and logistic kernel-machine approach was applied to test the cumulative effect of multiple SNPs as a group with non-PV triggers and LA scar. False discovery rate (FDR) was computed for all candidate SNPs to address multiple testing. RESULTS: SNPs rs6599230 and rs6843082 were inversely associated (OR 0.68, p=0.04, and 0.62, p=0.01, respectively) whereas rs1448817 (OR 1.74, p=0.04) and rs7193343 (OR 1.66, p=0.02) predicted higher risk of non-PV triggers. Genotypes for rs6599230 and rs6843082 conferred 51 % reduction in the odds for non-PV triggers (combined OR 0.49, p=0.019), while rs1448817 and rs7193343 demonstrated a combined OR of 1.93, p=0.025. FDR was controlled at 16 % to adjust for multiple testing. For LA scar, inverse association was observed with rs1448817 (OR 0.29, p=0.006), rs17042171 (OR 0.27, p=0.032), rs3807989 (OR 0.54, p=0.017), and rs6843082 (OR 0.56, p=0.009). Two SNPs were associated with increased scar risk: rs17375901 (OR 3.68, p=0.03) and rs7193343 (OR 1.74, p=0.037). For global association of SNPs with left atrial scar FDR was controlled at ≤10 % to adjust for multiple testing. CONCLUSIONS: This study has a strong clinical significance as it provides important insights into the molecular basis of pertinent therapeutic targets. Our findings demonstrate that the presence of certain genetic polymorphisms increases the risk of scar and non-PV triggers in AF patients. Therefore, PVAI alone will not be enough to eliminate the arrhythmia and the operators may need to identify and isolate the non-PV foci to maximize procedural success in patients carrying these risk variants. Clinical trial registration clinicaltrials.gov (NCT01751607).

Feasibility and safety of uninterrupted periprocedural apixaban administration in patients undergoing radiofrequency catheter ablation for atrial fibrillation: Results from a multicenter study.

BACKGROUND: Periprocedural anticoagulation management with uninterrupted warfarin and a "therapeutic" international normalized ratio is the best approach for reducing both thromboembolic and bleeding complications in the setting of catheter ablation for atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to evaluate the safety and feasibility of uninterrupted apixaban in this setting. METHODS: This was a prospective multicenter registry of AF patients undergoing radiofrequency catheter ablation at 4 institutions in United States and Europe with uninterrupted apixaban. These patients were compared with an equal number of patients, matched for age, gender, and type of AF, undergoing AF ablation on uninterrupted warfarin. The apixaban group was comprised of consecutive patients who had taken their last dose of apixaban the morning of the procedure. A subset of 29 patients in the apixaban group underwent diffusion magnetic resonance imaging (dMRI) to detect silent cerebral ischemia. RESULTS: A total of 400 patients (200 patients in each group) were included in the study. The average age was 65.9 ± 9.9 years, 286 (71.5%) were male, and 334 (83.5%) had nonparoxysmal AF. There were no statistical differences with regard to major complications (1% vs 0.5%, P = 1), minor complications (3.5% vs 2.5%, P = .56), or total bleeding complications (4.5% vs 3%, P = .43) between the apixaban and warfarin groups. There were no symptomatic thromboembolic complications. All dMRIs were negative for "new" silent cerebral ischemia in the apixaban group. CONCLUSION: Uninterrupted apixaban administration in patients undergoing AF ablation seems to be feasible and effective in preventing clinical and silent thromboembolic events without increasing the risk of major bleeding.