A Matched-Cohort Analysis of Outcomes in Patients with Hereditary Hemochromatosis After Anterior Cervical Discectomy and Fusion.

BACKGROUND: Hereditary hemochromatosis (HH) is a common autosomal recessive disorder. This disease affects gut iron transport, leading to iron overload, which affects immune function, coagulation mechanics, and bone health. Within the spine, HH contributes to decreased bone mineral density and accelerated intervertebral disc degeneration. The purpose of this study was to discover the differences in the rates of common 90-day postoperative complications and 1-year and 2-year surgical outcomes in patients with and without HH after anterior cervical discectomy and fusion (ACDF). METHODS: Using the PearlDiver database, patients with active diagnoses of HH before ACDF were matched to patients without HH using a 1:5 ratio on the basis of age, sex, body mass index, and comorbidities. Postoperative complications were assessed at 90 days, and 1-year and 2-year surgical outcomes were assessed. All outcomes and complications were analyzed using multivariate logistic regression with significance achieved at P < 0.05. RESULTS: Patients with HH had significantly higher rates of 1-year and 2-year reoperation rates compared with patients without HH (29.19% vs. 3.94% and 37.1% vs. 5.93%, respectively; P < 0.001). The rates of 90-day postoperative complications significantly increased in patients with HH including dysphagia, pneumonia, cerebrovascular accident, deep vein thrombosis, acute kidney injury, urinary tract infection, hyponatremia, surgical site infection, iatrogenic deformity, emergency department visit, and hospital readmission. CONCLUSIONS: Patients with HH undergoing ACDF showed increased 90-day postoperative complications and significantly increased rates of 1-year and 2-year reoperation compared with patients without HH. These findings suggest that iron overload may contribute to adverse outcomes in patients with HH undergoing 1-level and 2-level ACDF.

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.

Increased rates of spinal fusion surgery in patients with hereditary hemochromatosis: a five-year propensity matched cohort analysis.

OBJECT: Spinal arthropathy is associated with hereditary hemochromatosis and has been linked to calcium pyrophosphate dehydrate crystal deposition (CPPD) which resembles ankylosing spondylitis on radiograph, yet lacks clinical findings of inflammatory spinal arthritis. The aim of our study was to assess the use of spinal surgery and its outcomes in the US inpatient population with hereditary hemochromatosis from 2012 to 2016 by using the US Nationwide Inpatient Sample (NIS) database. METHODS: The observational retrospective cohort study uses the NIS 2012 to 2016. All patients with hereditary hemochromatosis were included using International Classification of Diseases 9th and 10th revisions, Clinical Modification codes. The cohort was stratified according to having undergone spinal surgery and substratified by the type of surgery. The primary outcome was determining the use of spinal surgery in patients with hereditary hemochromatosis. Secondary outcomes were determining length of hospital stay and total hospital charges and costs. RESULTS: A total of 39 780 patients with hereditary hemochromatosis were identified and propensity matched to nonhereditary hemochromatosis controls. The mean patient age was 61 years, and 65% were females. For the primary outcome patients with hereditary hemochromatosis underwent significantly more spinal fusion surgery compared to patients without hereditary hemochromatosis odds of 2.13 (P = 0.05). While there was no difference in mean LOS, or costs, patients with hereditary hemochromatosis had higher hospital charges. CONCLUSION: Hereditary hemochromatosis is associated with higher odds of spinal fusion. It is a major complication not improved by phlebotomy, and there are currently no therapies to prevent this joint disease.

Mechanical sensitivity of red blood cells improves in individuals with hemochromatosis following venesection therapy.

BACKGROUND: Individuals with hereditary hemochromatosis (HH) receive frequent blood withdrawals (ie, venesections) as part of their primary treatment to assist in normalizing blood iron levels. It remains unclear whether this source of blood is suitable for use in blood product development, as current data indicate that red blood cell (RBC) deformability, both before and after shear stress exposure, is impaired in individuals with HH, relative to healthy controls. Given that venesection therapy is known to significantly reduce circulating iron levels in individuals with HH, the current study examined whether venesection therapy is effective at improving RBC mechanical properties, both before and after shear stress exposure, in individuals with HH. STUDY DESIGN AND METHODS: Blood samples were initially collected from untreated HH patients (age, 61 ± 9 years; 14% female) undergoing their first venesection, and then again during their second (approx. 9 weeks later) and third (approx. 16 weeks later) venesections. RBC deformability was measured at each time point with a commercial ektacytometer. Moreover, to determine cell responses to mechanical stimuli, the mechanical sensitivity of blood samples was determined at each time point. RESULTS: The salient findings indicate that venesection therapy used for managing plasma ferritin concentration significantly improves the cellular deformability of RBC in individuals with HH. Further, the sensitivity of RBC to supraphysiological mechanical stress is decreased (ie, improved) in a dose-response fashion with routine venesection. CONCLUSION: While cellular mechanics of RBC from individuals with HH are impaired when untreated, venesection therapy significantly improves cellular properties of RBC, supporting the use of venesections in blood product development from individuals with well-managed HH.

Hereditary hemochromatosis is associated with increased use of joint replacement surgery: Results of a nationwide analysis.

BACKGROUND: Hereditary hemochromatosis (HH) may lead to iron deposition-mediated arthropathy, causing progressive joint degeneration, necessitating replacement arthroplasty. Studies have noted an increased need for replacement arthroplasty in patients with HH. We aimed to compare the use of replacement arthroplasty and inpatient economic burden in patients with and without HH. METHODS: For our retrospective cohort study, we used the 2014 Nationwide Inpatient Sample. Patients with an International Classification of Diseases, Ninth Revision code for HH were included. The primary outcome was use of replacement arthroplasty; secondary outcomes were hospital length of stay, hospital costs, and total hospitalization charges. Multivariate logistic regression yielded confounder-adjusted odds ratios (ORs) and means. RESULTS: Of 18,250 patients with HH, 7,483 (41.0%) were women and 1,155 (6.3%) underwent replacement arthroplasty. Mean (SD) age for patients with HH and arthroplasty was 66 (18) years. The percentage of patients with HH who underwent replacement arthroplasty was higher than those without HH (3.4%; P<.01). On multivariate analysis, young-adult females and elderly patients with HH were more likely to undergo replacement arthroplasty compared to those without HH of the corresponding gender and age group. Mean length of stay, hospital costs, and total hospitalization charges were increased only in young adult females. CONCLUSIONS: HH is associated with increased odds of replacement arthroplasty, particularly in the elderly, which can potentially suggest faster arthropathy progression in this age group and should raise awareness in clinicians taking care of patients with HH. Future research should identify factors mediating arthropathy progression in patients with HH.

Contemporary Total Hip and Total Knee Arthroplasty Results in Patients with Hemochromatosis.

BACKGROUND: Hemochromatosis can result in metabolic bone pathology (due to excessive iron absorption) and degenerative joint disease, leading to total joint arthroplasties. The aim of this study is to analyze the survivorship, complications, radiographic results, and clinical outcomes of patients with hemochromatosis who received either a total hip arthroplasty (THA) or a total knee arthroplasty (TKA). METHODS: We identified 34 lower extremity arthroplasties in 29 patients with hemochromatosis performed between 2000 and 2016. There were 17 primary THAs in 15 patients and 17 primary TKAs in 14 patients. Mean age at arthroplasty was 63 years with 76% being male. The mean body mass index was 28 kg/m2. Mean follow-up was 5 years. RESULTS: The survivorship free from any revision for THAs was 94% at 10 years. One patient was revised for aseptic loosening of the femoral stem at 6 months. In THA patients, no infections, no other complications, and no radiographic evidence of aseptic loosening were identified. Harris Hip Scores improved from a mean of 55 preoperatively to 94 postoperatively (P < .001). The survivorship free from any revision for TKAs was 100% at 10 years. Two patients (12%) developed acquired idiopathic stiffness postoperatively; no infections were identified. There was no radiographic evidence of aseptic loosening in any TKA. Knee Society Scores improved from a mean of 61 preoperatively to 94 postoperatively (P < .001). CONCLUSION: This study found excellent survivorship, significant improvements in clinical outcomes, and a very low complication profile for both THA and TKA in patients with hemochromatosis.

HFE hemochromatosis screening in patients with severe hip osteoarthritis: A prospective cross-sectional study.

OBJECTIVE: Despite the high frequency of HFE gene mutations in Western Europe, widespread screening for HFE hemochromatosis is not recommended due to its variable phenotype. Joint pain and a premature osteoarthritis-like disease including the hip joints are the most frequent manifestation in patients with HFE hemochromatosis and iron overload. Therefore, screening of patients with severe osteoarthritis of the hip could identify patients with HFE hemochromatosis. METHODS: In this prospective cross-sectional study, 940 patients aged <70 years with end-stage osteoarthritis of the hip undergoing elective joint replacement surgery were screened for HFE hemochromatosis and compared to age- and sex-matched controls. RESULTS: No greater prevalence of C282Y homozygosity mutation or elevated serum ferritin or transferrin saturation levels was found in the study cohort with severe osteoarthritis of the hip than in controls from the general population. CONCLUSION: Our screening approach could not identify an increased prevalence of HFE gene mutations and iron overload in younger patients with severe osteoarthritis of the hip.

From Death to Health in 30 Days: A Hemochromatosis Case Report.

BACKGROUND: Heredity hemochromatosis (HH) is an underdiagnosed genetic disease that can lead to life-threatening multisystem organ failure. Identifying and treating HH early can prevent the progression of the disease. CASE PRESENTATION: For a 60-year-old white patient without obvious symptoms, it was a revelation to discover that he had HH. This patient, although receiving evidence-based care, ultimately required a liver transplant. As his condition deteriorated, the plan for this patient and his family involved working within an interdisciplinary team that included nurse practitioners and intensive care unit nurses. DISCUSSION: The uniqueness of this case illustrates the crucial role of a health care team that persisted in differentiating the patient's diagnosis and continued to sustain both physical and emotional care throughout his hospitalization despite a poor prognosis. The patient felt support from this team during the course of his illness, from requiring life-supporting care in intensive care unit to returning home and resuming his normal activities of daily living.

Assessing the Non-tumorous Liver: Implications for Patient Management and Surgical Therapy.

INTRODUCTION: Hepatic resection is performed for various benign and malignant liver tumors. Over the last several decades, there have been improvements in the surgical technique and postoperative care of patients undergoing liver surgery. Despite this, liver failure following an extended hepatic resection remains a critical potential postoperative complication. Patients with underlying parenchymal liver diseases are at particular risk of liver failure due to impaired liver regeneration with an associated mortality risk as high as 60 to 90%. In addition, live donor liver transplantation requires a thorough presurgical assessment of the donor liver to minimize the risk of postoperative complications. RESULTS AND CONCLUSION: Recently, cross-sectional imaging assessment of diffuse liver diseases has gained momentum due to its ability to provide both anatomical and functional assessments of normal and abnormal tissues. Various imaging techniques are being employed to assess diffuse liver diseases including magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound (US). MRI has the ability to detect abnormal intracellular and molecular processes and tissue architecture. CT has a high spatial resolution, while US provides real-time imaging, is inexpensive, and readily available. We herein review current state-of-the-art techniques to assess the underlying non-tumorous liver. Specifically, we summarize current approaches to evaluating diffuse liver diseases including fatty liver alcoholic or non-alcoholic (NAFLD, AFLD), hepatic fibrosis (HF), and iron deposition (ID) with a focus on advanced imaging techniques for non-invasive assessment along with their implications for patient management. In addition, the role of and techniques to assess hepatic volume in hepatic surgery are discussed.

Nonrheumatoid Arthritis of the Hand.

Arthropathy of the hand is commonly encountered. Contributing factors such as aging, trauma, and systemic illness all may have a role in the evolution of this pathology. Besides rheumatoid arthritis, other diseases affect the small joints of the hand. A review of nonrheumatoid hand arthropathies is beneficial for clinicians to recognize these problems.

Heart and heart-liver transplantation in patients with hemochromatosis.

BACKGROUND: Hemochromatosis predisposes to dilated or restrictive cardiomyopathy which can progress to end-stage heart failure, requiring the use of advanced heart therapies including heart (HT) and heart liver (HLT) transplantation. Little is known about the characteristics and outcomes of these patients. METHODS AND RESULTS: We queried the United Network for Organ Sharing (UNOS) registry for all patients listed for HT or HLT for a diagnosis of 'hemochromatosis' between 1987 and 2014. Waitlist and post-transplantation outcomes were compared between patients with hemochromatosis (HT vs HLT) and other etiologies. Of the 81,356 adults listed for heart transplantation, 23 patients with hemochromatosis were identified (16 listed for HLT; and 7 listed for HT). Compared with other etiologies, HC patients were younger (39 vs 51years, p<0.0001), and more likely to need inotropes (56.5% vs 25.6%, p=0.003) and mechanical ventilation (13% vs 3.4%, p=0.041). Cumulative hazards of waitlist mortality or delisting were higher in hemochromatosis patients than for other etiologies of heart failure (p<0.001). There were 4 HT and 4 HLT during the study period. Post-transplantation, patients with HC had a 1- and 2-year cumulative survival of 88% and 75%, respectively. CONCLUSIONS: Both HT and HLT are viable options for patients with hemochromatosis. Patients with hemochromatosis are younger with increased wait-list mortality compared with other etiologies.

Examining the clinical use of hemochromatosis genetic testing.

BACKGROUND: Hereditary hemochromatosis leads to an increased lifetime risk for end-organ damage due to excess iron deposition. Guidelines recommend that genetic testing be performed in patients with clinical suspicion of iron overload accompanied by elevated serum ferritin and transferrin saturation levels. OBJECTIVE: To evaluate guideline adherence and the clinical and economic impact of HFE genetic testing. METHODS: The electronic charts of patients submitted for HFE testing in 2012 were reviewed for genetic testing results, biochemical markers of iron overload and clinical history of phlebotomy. RESULTS: A total of 664 samples were sent for testing, with clinical, biochemical and phlebotomy data available for 160 patients. A positive C282Y homozygote or C282Y/H63D compound heterozygote test result was observed in 18% of patients. Patients with an at-risk HFE genotype had significantly higher iron saturation, serum iron and hemoglobin (P<0.001), without higher ferritin or liver enzyme levels. Fifty percent of patients referred for testing did not have biochemical evidence of iron overload (transferrin saturation >45% and ferritin level >300 µg/L). Patients were four times more likely to undergo phlebotomy if they were gene test positive (RR 4.29 [95% CI 2.35 to 7.83]; P<0.00001). DISCUSSION: One-half of patients referred for testing did not exhibit biochemical evidence of iron overload. Many patients with biochemical evidence of iron overload, but with negative genetic test results, did not undergo phlebotomy. A requisition to determine clinical indication for testing may reduce the use of the HFE genetic test. Finally, improvement of current genetic test characteristics would improve rationale for the test. CONCLUSION: A significant proportion of hemochromatosis genetic testing does not adhere to current guidelines and would not alter patient management.

Liver transplantation for neonatal hemochromatosis: analysis of the UNOS database.

NH is the most common identifiable cause of ALF in the neonate. LT is the definitive treatment for neonates with NH who have failed medical therapy. Our aim was to determine the outcomes of LT in infants with NH. Patients (less than one yr of age) with NH who were listed for LT and patients who underwent LT between 1994 and 2013 were identified from the UNOS database for analysis. Risk factors for death and graft loss were analyzed by multivariate logistic regression. Thirty-eight infants with NH with a total of 43 transplants were identified. One- and five-yr patient and graft survival were 84.2%, 81.6%, 71.1%, and 68.4%, respectively. The outcomes for NH were not significantly different when compared to the same age-matched recipients with other causes of ALF. There were no statistically significant risk factors identified for graft loss or death. Ninety infants with NH were listed for LT. Reasons for removal included transplanted (49%), death (27%), too sick to transplant (7%), and improved status (13%). LT for infants with NH has a high rate of graft loss and death; however, outcomes are comparable to the same age-matched recipients with other causes of ALF.

Liver transplantation normalizes serum hepcidin level and cures iron metabolism alterations in HFE hemochromatosis.

UNLABELLED: Defects in human hemochromatosis protein (HFE) cause iron overload due to reduced hepatic hepcidin secretion. Liver transplantation (LT) is a key treatment for potential complications from HFE-related hereditary hemochromatosis (HH). This study evaluated hepcidin secretion and iron burden after LT to elucidate HH pathophysiology. Patients (n=18) homozygous for the p.Cys282Tyr mutation in the HFE gene underwent LT between 1999 and 2008. Serum iron, serum hepcidin, and hepatic iron concentrations were determined before LT and at the end of follow-up (median 57 months). Mortality and causes of death were determined. Survival was compared to that of the overall patient population that received LT. Before LT, serum hepcidin levels were low (0.54 ± 2.5 nmol/L; normal range: 4-30 nmol/L). After LT, 11 patients had iron evaluations; none received iron depletion therapy; all had normal transferrin saturation. The mean serum ferritin was 185 (± 99) µg/L. Magnetic resonance imaging showed that iron overload was absent in nine patients, mild in one patient with metabolic syndrome, and high (180 µmol/g) in one patient with hereditary spherocytosis discovered after LT. At the end of follow-up, serum hepcidin was normal in 10 patients (11.12 ± 7.6 nmol/L; P<0.05) and low in one patient with iron deficiency anemia. Survival was 83% and 67% at 1 and 5 years, respectively. Survival was similar for patients with HH and patients that received LT for other causes. CONCLUSION: In HH, LT normalized hepcidin secretion and prevented recurrence of hepatic iron overload. Survival was similar to that of patients who received LTs for other liver diseases.