ABSTRACT
BACKGROUND AND AIM: Patients with chronic granulomatous disease (CGD) may develop inflammatory bowel disease (IBD). Characterization of small bowel disease in this cohort is scarce. Here, we sought to determine the prevalence and characteristics of small bowel disease and evaluate the clinical utility of video capsule endoscopy (VCE) for its diagnosis. METHODS: A retrospective study was performed on patients with CGD who were evaluated for gastrointestinal disease with VCE as a part of ongoing natural history studies at a single academic center. VCEs were reviewed for inflammatory findings and severity of disease utilizing the Capsule Endoscopy Crohn's Disease Activity Index. Radiographic studies and endoscopies performed within 30 days of VCE were compared with small bowel inflammatory findings. RESULTS: Twenty-six VCEs corresponding to 25 patients were found. The majority of patients were male and White; mean age was 28 years old. The majority (85%) demonstrated presence of small bowel inflammatory findings on VCE including strictures, ulcers, erosions, and erythema. Duodenal and ileal inflammatory disease on endoscopy did not correlate with disease on VCE. Moderate-severe colonic disease correlated with moderate-severe disease on VCE. Radiography did not correlate with disease on VCE. Prolonged small bowel transit time correlated with moderate-severe small bowel disease. CONCLUSIONS: Small bowel IBD was highly prevalent in this cohort of patients with CGD. Limitations included small sample size. Given that radiology and duodenal/ileal disease did not correlate with VCE findings, VCE-driven investigation of small bowel disease should be considered in patients with CGD-associated IBD, particularly those with colonic disease.
Subject(s)
Capsule Endoscopy , Colonic Diseases , Crohn Disease , Granulomatous Disease, Chronic , Inflammatory Bowel Diseases , Humans , Male , Female , Adult , Crohn Disease/complications , Crohn Disease/diagnosis , Crohn Disease/epidemiology , Retrospective Studies , Prevalence , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/epidemiologyABSTRACT
Galanin (Gal) is a peptide with a role in neuroendocrine regulation of the liver. In this study, we assessed the role of Gal and its receptors, Gal receptor 1 (GalR1) and Gal receptor 2 (GalR2), in cholangiocyte proliferation and liver fibrosis in multidrug resistance protein 2 knockout (Mdr2KO) mice as a model of chronic hepatic cholestasis. The distribution of Gal, GalR1, and GalR2 in specific liver cell types was assessed by laser-capture microdissection and confocal microscopy. Galanin immunoreactivity was detected in cholangiocytes, hepatic stellate cells (HSCs), and hepatocytes. Cholangiocytes expressed GalR1, whereas HSCs and hepatocytes expressed GalR2. Strategies were used to either stimulate or block GalR1 and GalR2 in FVB/N (wild-type) and Mdr2KO mice and measure biliary hyperplasia and hepatic fibrosis by quantitative PCR and immunostaining of specific markers. Galanin treatment increased cholangiocyte proliferation and fibrogenesis in both FVB/N and Mdr2KO mice. Suppression of GalR1, GalR2, or both receptors in Mdr2KO mice resulted in reduced bile duct mass and hepatic fibrosis. In vitro knockdown of GalR1 in cholangiocytes reduced α-smooth muscle actin expression in LX-2 cells treated with cholangiocyte-conditioned media. A GalR2 antagonist inhibited HSC activation when Gal was administered directly to LX-2 cells, but not via cholangiocyte-conditioned media. These data demonstrate that Gal contributes not only to cholangiocyte proliferation but also to liver fibrogenesis via the coordinate activation of GalR1 in cholangiocytes and GalR2 in HSCs.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B/genetics , Cholestasis/metabolism , Galanin/metabolism , Liver Cirrhosis/metabolism , Receptor, Galanin, Type 1/metabolism , Receptor, Galanin, Type 2/metabolism , Animals , Bile Ducts/metabolism , Cell Proliferation , Cholestasis/pathology , Disease Models, Animal , Epithelial Cells/metabolism , Female , Galanin/genetics , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/pathology , Liver/metabolism , Liver/pathology , Liver Cirrhosis/pathology , Mice , Mice, Knockout , Receptor, Galanin, Type 1/genetics , Receptor, Galanin, Type 2/genetics , ATP-Binding Cassette Sub-Family B Member 4ABSTRACT
BACKGROUND: Anemia is a common systemic complication of inflammatory bowel disease (IBD) and is associated with worse disease outcomes, quality of life, and higher healthcare costs. AIMS: The purpose of this study was to determine how anemia severity impacts healthcare resource utilization and if treatment of anemia was associated with reduced utilization and costs. METHODS: Retrospective chart review of adult patients managed by gastroenterology between 2014 and 2018 at a tertiary referral center. RESULTS: The records of 1763 patients with IBD were included in the analysis, with 966 (55%) patients with CD, 799 (44%) with UC, and 18 (1%) with unspecified IBD. Of these patients, 951 (54%) had anemia. Patients with anemia had significantly more hospitalizations, increased length of stays, more ER, GI, and PCP visits, as well as higher costs when compared to patients with IBD without anemia. Patients with more severe anemia had more healthcare utilization and incurred even higher total costs. Treatment with IV or oral iron did not lower overall utilization or costs, when compared to patients with anemia who did not receive treatment (p < 0.0001). CONCLUSIONS: Our results demonstrate that the presence of anemia is correlated with increased resource utilization in patients with IBD, with increase in anemia severity associated with higher utilization and costs. Anemia has been associated with increased disease activity and could represent a marker of more severe disease, possibly explaining these associations. Our results suggest that treating anemia is associated with increased resource utilization; however, further research is needed to investigate this relationship.
Subject(s)
Anemia/complications , Anemia/pathology , Health Care Costs , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/economics , Patient Acceptance of Health Care , Adult , Anemia/economics , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
The purpose of this study is to determine if the United States Preventive Services Task Force (USPSTF) screening guideline for osteoporosis identifies women under the age of 65 with osteoporosis needing bone mineral density (BMD) testing. If the Fracture Risk Assessment Tool (FRAX) tool fails to identify women under the age of 65 with undiagnosed osteoporosis, then diagnosis and treatment are delayed, potentially leading to increased fractures and morbidity. Another aim of this study is to characterize women under the age of 65 with osteoporosis that FRAX fails to identify and provide descriptive data on our study population. A retrospective chart review was completed between 2012 and 2018. We extracted data for 113 women ≤ 65-years with osteoporosis confirmed by BMD or fractures. Major osteoporotic fracture (MOF) risk calculation without BMD by FRAX of 9.3% or greater (high risk group) was found in 51 (45.1%) of patients. Osteoporosis by T-score < 2.5 was evident in 102 (90%) of patients. Previous osteoporotic fractures were noted in 29 (25.7%) of patients. The average age of women in the high-risk group was 58 years and 55 years in the low-risk group. The sensitivity of FRAX for identifying women with a T-score <-2.5 was 40%. The sensitivity of FRAX for identifying women with a history of fracture was 32%. The sensitivity of FRAX for identifying women with a T-score <-2.5 or identifying women with a history of fracture was 32%. These results demonstrate that the FRAX tool alone (USPSTF recommendation) fails to identify many women under the age of 65 with osteoporosis in need of BMD testing. Over half of women would not have had a BMD performed based on guidelines for screening BMD in women <65. Further study is needed to characterize women under the age of 65 with osteoporosis with a FRAX MOF risk less than 9.3%.
Subject(s)
Bone Density , Osteoporotic Fractures , Absorptiometry, Photon , Female , Humans , Middle Aged , Osteoporotic Fractures/diagnostic imaging , Osteoporotic Fractures/epidemiology , Retrospective Studies , Risk Assessment , Risk FactorsABSTRACT
Alcohol-associated liver disease is a common and severe sequela of excessive alcohol use; effective treatment requires attention to both liver disease and underlying alcohol use disorder (AUD). Alcohol withdrawal syndrome (AWS) can be dangerous, is a common barrier to AUD recovery, and may complicate inpatient admissions for liver-related complications. Hepatologists can address these comorbid conditions by learning to accurately stage alcohol-associated liver disease, identify AUD using standardized screening tools (eg, Alcohol Use Disorder Identification Test), and assess risk for and symptoms of AWS. Depending on the severity, alcohol withdrawal often merits admission to a monitored setting, where symptom-triggered administration of benzodiazepines based on standardized scoring protocols is often the most effective approach to management. For patients with severe liver disease, selection of benzodiazepines with less dependence on hepatic metabolism (eg, lorazepam) is advisable. Severe alcohol withdrawal often requires a "front-loaded" approach with higher dosing, as well as intensive monitoring. Distinguishing between alcohol withdrawal delirium and HE is important, though it can be difficult, and can be guided by differentiating clinical characteristics, including time to onset and activity level. There is little data on the use of adjuvant medications, including anticonvulsants, dexmedetomidine, or propofol, in this patient population. Beyond the treatment of AWS, inpatient admission and outpatient hepatology visits offer opportunities to engage in planning for ongoing management of AUD, including initiation of medications for AUD and referral to additional recovery supports. Hepatologists trained to identify AUD, alcohol-associated liver disease, and risk for AWS can proactively address these issues, ensuring that patients' AWS is managed safely and effectively and supporting planning for long-term recovery.
Subject(s)
Alcoholism , Liver Diseases, Alcoholic , Substance Withdrawal Syndrome , Humans , Alcoholism/complications , Alcoholism/diagnosis , Alcoholism/therapy , Substance Withdrawal Syndrome/diagnosis , Substance Withdrawal Syndrome/drug therapy , Liver Diseases, Alcoholic/complications , Liver Diseases, Alcoholic/diagnosis , Liver Diseases, Alcoholic/therapy , Benzodiazepines/therapeutic use , CognitionABSTRACT
BACKGROUND: Alcohol-associated hepatitis (AH) is a severe inflammatory form of alcohol-associated liver disease (ALD) that carries a high mortality rate. Early liver transplantation for severe AH is increasingly available. However, specific criteria for referral and selection remain a subject of debate. AIMS: To provide a narrative review of the natural history, diagnostic criteria and indications for referral for early liver transplantation for severe AH. METHODS: We searched PubMed for articles published through August 2023. Key search terms were 'alcoholic hepatitis,' 'alcohol-associated hepatitis,' 'abstinence,' 'alcohol relapse,' and 'liver transplantation.' RESULTS: Previously, a six-month period of alcohol abstinence was required before patients with ALD were considered for liver transplantation. However, studies in recent years have demonstrated that, among carefully selected patients, patients who received early transplants have much higher survival rates than patients with similarly severe disease who did not undergo transplants (77% vs. 23%). Despite these successes, early liver transplantation remains controversial, as these patients have typically not undergone treatment for alcohol use disorder, with the ensuing risk of returning to alcohol use. CONCLUSIONS: While early liver transplantation for AH has survival benefits, many patients would not have received treatment for alcohol use disorder. An integrated approach to evaluating candidacy for early liver transplantation is needed.
Subject(s)
Alcoholism , Hepatitis, Alcoholic , Liver Diseases, Alcoholic , Liver Transplantation , Humans , Hepatitis, Alcoholic/diagnosis , Hepatitis, Alcoholic/surgery , Hepatitis, Alcoholic/complications , Alcoholism/complications , Liver Transplantation/adverse effects , Patient Selection , Liver Diseases, Alcoholic/complicationsABSTRACT
BACKGROUND: Alcohol cessation is the only intervention that both prevents and halts the progressions of alcohol-associated liver disease. The aim of this study was to assess the relationship between a return to alcohol use and consultation with hepatology in treatment-seeking patients with alcohol use disorder (AUD). METHODS: Two hundred forty-two patients with AUD were enrolled in an inpatient treatment program, with hepatology consultation provided for 143 (59%) patients at the request of the primary team. Patients not seen by hepatology served as controls. The primary outcome was any alcohol use after discharge assessed using AUDIT-C at 26 weeks after discharge. RESULTS: For the primary endpoint, AUDIT at week 26, 61% of the hepatology group and 28% of the controls completed the questionnaire (p=0.07). For the secondary endpoint at week 52, these numbers were 22% and 11% (p = 0.6). At week 26, 39 (45%) patients in the hepatology group versus 31 (70%) controls (p = 0.006) returned to alcohol use. Patients evaluated by hepatology had decreased rates of hazardous alcohol use compared to controls, with 36 (41%) versus 29 (66%) (p = 0.008) of the patients, respectively, reporting hazardous use. There were no significant differences in baseline characteristics between groups and no difference in rates of prescribing AUD therapy. There was no difference in outcomes at 52 weeks. CONCLUSIONS: Patients evaluated by hepatology had significantly lower rates of return to alcohol use and lower rates of hazardous drinking at 26 weeks but not at 52 weeks. These findings suggest that hepatology evaluation during inpatient treatment of AUD may lead to decreased rates of early return to alcohol use.
Subject(s)
Alcoholism , Gastroenterology , Liver Diseases, Alcoholic , Humans , Alcoholism/epidemiology , Alcoholism/therapy , Patient Discharge , Inpatients , Liver Diseases, Alcoholic/therapy , Referral and ConsultationABSTRACT
INTRODUCTION: Chronic Hepatitis D virus (HDV) infection remains an important global public health problem, with a changing epidemiological landscape over the past decade along with widespread implementation of hepatitis B vaccination and human migration. The landscape of HDV treatments has been changing, with therapies that have been under development for the last decade now in late stage clinical trials. The anticipated availability of these new therapies will hopefully replace the current therapies which are minimally effective. AREAS COVERED: This narrative review discusses the clinical course, screening and diagnosis, transmission risk factors, epidemiology, current and investigational therapies, and liver transplantation in HDV. Literature review was performed using PubMed and ClinicalTrials.gov and includes relevant articles from 1977 to 2022. EXPERT OPINION: HDV infection is an important global public health issue with a true prevalence that is still unknown. The distribution of HDV infection has changed globally with the availability of HBV vaccination and patterns of human migration. As HDV infection is associated with accelerated disease courses and poor outcomes, the global community needs to agree upon a uniform HDV screening strategy to understand the truth of global prevalence such that new therapies can target appropriate individuals as they become available in the future.
Subject(s)
Hepatitis B , Hepatitis D, Chronic , Hepatitis D , Liver Transplantation , Humans , Hepatitis D, Chronic/drug therapy , Hepatitis D, Chronic/epidemiology , Hepatitis D/diagnosis , Hepatitis D/drug therapy , Hepatitis D/epidemiology , Hepatitis Delta Virus , Risk Factors , Hepatitis B virus , Hepatitis B/diagnosis , Hepatitis B/drug therapy , Hepatitis B/epidemiologyABSTRACT
Content available: Audio Recording.
ABSTRACT
Hemophagocytic lymphohistiocytosis is a syndrome of excessive immune activation frequently attributed to infection. We report a case of hemophagocytic lymphohistiocytosis secondary to hepatitis B in a patient with human immunodeficiency virus coinfection and subsequent liver failure.
ABSTRACT
Achalasia is a rare condition that most often presents with progressive dysphagia to solids and liquids. We report a case of achalasia presenting with acute respiratory failure and hemodynamic instability requiring both ventilator and vasopressor support because of extrinsic compression of the airway and left atrium by a dilated and fluid-filled esophagus. This is the first case reported of achalasia, causing both left atrial compression and airway compression.