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Quiroz-Aldave JE, Gamarra-Osorio ER, Durand-Vásquez MDC, Rafael-Robles LDP, Gonzáles-Yovera JG, Quispe-Flores MA, Concepción-Urteaga LA, Román-González A, Paz-Ibarra J, Concepción-Zavaleta MJ. From liver to hormones: The endocrine consequences of cirrhosis. World J Gastroenterol 2024; 30:1073-1095. [PMID: 38577191 PMCID: PMC10989500 DOI: 10.3748/wjg.v30.i9.1073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 01/02/2024] [Accepted: 02/06/2024] [Indexed: 03/06/2024] Open
Abstract
Hepatocrinology explores the intricate relationship between liver function and the endocrine system. Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption. Despite its importance, assessing endocrine issues in cirrhotic patients is frequently neglected. This article provides a comprehensive review of the epidemiology, pathophysiology, diagnosis, and treatment of endocrine disturbances in liver cirrhosis. The review was conducted using the PubMed/Medline, EMBASE, and Scielo databases, encompassing 172 articles. Liver cirrhosis is associated with endocrine disturbances, including diabetes, hypoglycemia, sarcopenia, thyroid dysfunction, hypogonadotropic hypogonadism, bone disease, adrenal insufficiency, growth hormone dysfunction, and secondary hyperaldosteronism. The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system, respectively. Sarcopenia can be assessed through imaging and functional tests, while other endocrine disorders are evaluated using hormonal assays and imaging studies. Treatment options include metformin, glucagon-like peptide-1 analogs, sodium-glucose co-transporter-2 inhibitors, and insulin, which are effective and safe for diabetes control. Established standards are followed for managing hypoglycemia, and hormone replacement therapy is often necessary for other endocrine dysfunctions. Liver transplantation can address some of these problems.
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Affiliation(s)
| | | | | | | | | | | | | | - Alejandro Román-González
- Department of Endocrinology, Hospital Universitario de San Vicente Fundación, Medellin 050010, Colombia
- Internal Medicine, Universidad de Antioquia, Medellín 050010, Colombia
| | - José Paz-Ibarra
- School of Medicine, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru
- Department of Endocrinology, Hospital Nacional Edgardo Rebagliati Martins, Lima 15072, Peru
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Wentworth BJ, Schliep M, Novicoff W, Henry ZH, Siragy HM. Basal cortisol levels do not predict adrenal responsiveness in acute decompensated cirrhosis. Eur J Gastroenterol Hepatol 2024; 36:238-244. [PMID: 38131427 PMCID: PMC10752291 DOI: 10.1097/meg.0000000000002694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2023]
Abstract
OBJECTIVE Morning total cortisol (TC) levels have been shown to predict adrenal dysfunction (AD) in the general population, but their utility in cirrhosis is unknown. METHODS A retrospective cohort study was performed including all noncritically ill patients at our institution between 2011 and 2022 admitted with acute decompensated cirrhosis who underwent standard-dose adrenocorticotropic hormone (ACTH) stimulation testing. Adrenal dysfunction was defined as an increase in TC (delta TC) level <9 µg/dl 60 minutes after ACTH dosing. Spearman correlation was utilized to assess the relationship between binding globulins and cortisol levels. Multivariate regression analysis was performed to determine if basal TC level or common clinical parameters were predictive of AD. RESULTS One hundred and nineteen patients were included, with a median model for end-stage liver disease score of 18. Albumin levels did not correlate with basal TC levels (ρ = 0.127; P = 0.169); basal TC did not correlate with delta TC (ρ = 0.050; P = 0.591). The degree of hypoalbuminemia did not alter these relationships. On multivariate regression, only albumin level [odds ratio (OR) = 0.418; 95% confidence interval (CI), 0.196-0.890; P = 0.024] and MELD score (OR, 1.094; 95% CI, 1.019-1.174; P = 0.014) were predictive of AD. Basal TC levels were not predictive of AD (OR = 0.991; 95% CI, 0.903-1.088; P = 0.855) or delta TC (β = 0.000; 95% CI -0.147 to 0.147; P = 0.999). CONCLUSION Baseline TC levels do not predict ACTH stimulation testing response in patients with acute decompensated cirrhosis. Clinicians should avoid utilizing an isolated morning cortisol result as a screening method for AD in this population.
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Affiliation(s)
- Brian J Wentworth
- Division of Gastroenterology & Hepatology, School of Medicine, University of Virginia, Charlottesville, VA
| | - Matthew Schliep
- Department of Medicine, School of Medicine, University of Virginia, Charlottesville, VA
| | - Wendy Novicoff
- Departments of Public Health Sciences and Orthopaedic Surgery, School of Medicine, University of Virginia Charlottesville, VA
| | - Zachary H Henry
- Division of Gastroenterology & Hepatology, School of Medicine, University of Virginia, Charlottesville, VA
| | - Helmy M Siragy
- Division of Endocrinology & Metabolism, School of Medicine, University of Virginia, Charlottesville, VA
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Badura K, Frąk W, Hajdys J, Majchrowicz G, Młynarska E, Rysz J, Franczyk B. Hepatorenal Syndrome-Novel Insights into Diagnostics and Treatment. Int J Mol Sci 2023; 24:17469. [PMID: 38139297 PMCID: PMC10744165 DOI: 10.3390/ijms242417469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/09/2023] [Accepted: 12/11/2023] [Indexed: 12/24/2023] Open
Abstract
Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the third most common cause of acute kidney injury, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of HRS. We discuss pathogenesis associated with HRS. Mechanisms such as dysfunction of the circulatory system, bacterial infection, inflammation, impaired renal autoregulation, circulatory, and others, which have been identified as critical pathways for development of HRS, have become easier to diagnose in recent years. Additionally, relatively recently, renal dysfunction biomarkers have been found indicating renal injury, which are involved in the pathophysiology of HRS. This review also summarizes the available information on the management of HRS, focusing on vasoconstrictive drugs, renal replacement therapy, and liver transplant together with currently being investigated novel therapies. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of HRS.
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Affiliation(s)
- Krzysztof Badura
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Weronika Frąk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Joanna Hajdys
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Gabriela Majchrowicz
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
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Bao R, Chen B, Pan J, Wang A, Yu H, Chen Q, Zhang Y, Wang T. Pseudohypoadrenalism, a subclinical cortisol metabolism disorder in hyperuricemia. Front Endocrinol (Lausanne) 2023; 14:1279205. [PMID: 38034015 PMCID: PMC10687422 DOI: 10.3389/fendo.2023.1279205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 10/31/2023] [Indexed: 12/02/2023] Open
Abstract
Background Hyperuricemia is a known risk factor of lipid metabolism disorder. However, the mechanisms have not been fully understood. Methods The serum samples from hyperuricemia subjects were used to analyze the correlation between serum uric acid and clinical characteristics. Hyperuricemia mice induced by potassium oxonate (PO) and adenine were used to explore glucocorticoid metabolism. Results In hyperuricemia patients, the levels of serum uric acid were positively correlated with the levels of γ-glutamyltransferase, associated with a cortisol metabolism disorder. In hyperuricemia state, the adrenal glands failed to respond to adrenocorticotropic hormone properly, leading to low cortisol, but not corticosterone production, and decreased mRNA levels of aldosterone synthase, 11β-hydroxylase, and 3β-hydroxysteroid dehydrogenase 1, three key enzymes for cortisol synthesis. The expression of both hepatic 5α-reductase and renal 11β-hydroxysteroid dehydrogenase 2 was significantly reduced, which led to low cortisol clearance. We denominated this cortisol metabolism disorder in hyperuricemia as pseudohypoadrenalism (PHAL). Conclusion PHAL increased exposure to the bioavailable cortisol in the liver, leading to local amplification of the biological action of corticosteroids. Unregulated biosynthesis pathway of bile acid expanded bile acid pool, and further aggravated cholestatic liver injury.
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Affiliation(s)
- Ruixia Bao
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, China
| | - Beibei Chen
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, China
| | - Jujie Pan
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, China
| | - Alexander Wang
- College of Education, University of Texas at Austin, Austin, TX, United States
| | - Haiyang Yu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, China
| | - Qian Chen
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, China
| | - Yi Zhang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, China
| | - Tao Wang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, China
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Hartl L, Simbrunner B, Jachs M, Wolf P, Bauer DJM, Scheiner B, Balcar L, Semmler G, Schwarz M, Marculescu R, Trauner M, Mandorfer M, Reiberger T. An impaired pituitary-adrenal signalling axis in stable cirrhosis is linked to worse prognosis. JHEP Rep 2023; 5:100789. [PMID: 37484210 PMCID: PMC10362733 DOI: 10.1016/j.jhepr.2023.100789] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 05/01/2023] [Accepted: 05/04/2023] [Indexed: 07/25/2023] Open
Abstract
Background & Aims Inadequate adrenal function has been described in patients with cirrhosis. We investigated (i) the pituitary-adrenal axis at different clinical stages and (ii) the clinical impact of decreased serum cortisol levels in stable patients with advanced chronic liver disease (ACLD). Methods We included 137 outpatients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement in the prospective VICIS study (NCT03267615). Patients were stratified into six clinical stages: S0: subclinical portal hypertension (PH) (HVPG 6-9 mmHg), S1: clinically significant PH (HVPG ≥10 mmHg) without varices, S2: presence of varices, S3: previous variceal bleeding, S4: previous non-bleeding decompensation, and S5: further decompensation. Results Fifty-one patients had compensated ACLD (S0: n = 13; S1: n = 12; S2: n = 26), whereas 86 patients had decompensated ACLD (S3: n = 7; S4: n = 46; S5: n = 33). Serum total cortisol (t-Cort) showed a strong correlation with estimated serum free cortisol (f-Cort; Spearman's ρ: 0.889). With progressive clinical stage, median ACTH levels (from S0: 44.0 pg/ml to S5: 20.0 pg/ml; p = 0.006), t-Cort (from S0: 13.9 μg/dl to S5: 9.2 μg/dl; p = 0.091), and cortisol binding globulin (from S0: 49.3 μg/ml to S5: 38.9 μg/ml; p <0.001) decreased, whereas f-Cort (p = 0.474) remained unchanged. Lower t-Cort levels independently predicted bacterial infections (asHR: 1.11; 95% CI: 1.04-1.19; p = 0.002), further decompensation (asHR: 1.08; 95% CI: 1.02-1.12; p = 0.008), acute-on-chronic liver failure (ACLF; asHR: 1.11; 95% CI: 1.04-1.19; p = 0.002), and liver-related death (asHR: 1.09; 95% CI: 1.01-1.18; p = 0.045). Conclusions The pituitary-ACTH-adrenal-cortisol axis is progressively suppressed with increasing severity of cirrhosis. Lower t-Cort is an independent risk factor for bacterial infections, further decompensation of ACLF, and liver-related mortality-even in stable outpatients with cirrhosis. Clinical trial number Vienna Cirrhosis Study (VICIS; NCT: NCT03267615). Impact and Implications In a cohort of stable outpatients, we observed progressive suppression of the pituitary-adrenal axis with increasing clinical stage of advanced chronic liver disease (ACLD). Increased levels of bile acids and systemic inflammation (assessed by interleukin-6 levels) could be involved in this suppression. Serum total cortisol (t-Cort) was strongly correlated with serum free cortisol (f-Cort) and lower t-Cort levels were independently associated with a higher risk of adverse clinical outcomes, including bacterial infections, further decompensation, acute-on-chronic liver failure, and liver-related death.
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Affiliation(s)
- Lukas Hartl
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Benedikt Simbrunner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mathias Jachs
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Peter Wolf
- Division of Endocrinology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - David Josef Maria Bauer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Lorenz Balcar
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Michael Schwarz
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Rodrig Marculescu
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
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Ibáñez-Samaniego L, Baines A, Bañares R. Afectación renal en la enfermedad hepática crónica avanzada. Síndrome hepatorrenal. MEDICINE - PROGRAMA DE FORMACIÓN MÉDICA CONTINUADA ACREDITADO 2023; 13:4841-4849. [DOI: 10.1016/j.med.2023.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Wentworth BJ, Schliep M, Novicoff W, Siragy HM, Geng CX, Henry ZH. Relative adrenal insufficiency in the non-critically ill patient with cirrhosis: A systematic review and meta-analysis. Liver Int 2023; 43:660-672. [PMID: 36354293 PMCID: PMC9974795 DOI: 10.1111/liv.15473] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 11/05/2022] [Accepted: 11/08/2022] [Indexed: 11/12/2022]
Abstract
BACKGROUND & AIMS Characterization of relative adrenal insufficiency (RAI) in cirrhosis is heterogeneous with regard to studied patient populations and diagnostic methodology. We aimed to describe the prevalence and prognostic importance of RAI in non-critically ill patients with cirrhosis. METHODS A systematic review and meta-analysis was performed using MeSH terms and Boolean operators to search five large databases (Ovid-MEDLINE, ScienceDirect, Web of Science, Cochrane Library and ClinicalTrials.gov). The population of interest was patients with cirrhosis and without critical illness. The primary outcome was the pooled prevalence of RAI as defined by a peak total cortisol level <18 μg/dl, delta total cortisol <9 μg/dl or composite of the two thresholds in response either a standard-dose or low-dose short synacthen test. Odds ratios and standardized mean differences from random-effects models estimated important clinical outcomes and patient characteristics by adrenal functional status. RESULTS Twenty-two studies were included in final analysis, comprising 1991 patients with cirrhosis. The pooled prevalence of RAI was 37% (95% CI 33-42%). The prevalence of RAI varied by Child-Pugh classification, type of stimulation test used, specific diagnostic threshold and by severity of illness. Ninety-day mortality was significantly higher in patients with RAI (OR 2.88, 95% CI 1.69-4.92, I2 = 15%, p < 0.001). CONCLUSIONS Relative adrenal insufficiency is highly prevalent in non-critically ill patients with cirrhosis and associated with increased mortality. Despite the proposed multifactorial pathogenesis, no studies to date have investigated therapeutic interventions in this specific population.
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Affiliation(s)
- Brian J Wentworth
- Division of Gastroenterology & Hepatology, School of Medicine, University of Virginia, Charlottesville, VA
| | - Matthew Schliep
- Department of Medicine, School of Medicine, University of Virginia, Charlottesville, VA
| | - Wendy Novicoff
- Departments of Public Health Sciences and Orthopaedic Surgery, School of Medicine, University of Virginia Charlottesville, VA
| | - Helmy M Siragy
- Division of Endocrinology & Metabolism, School of Medicine, University of Virginia, Charlottesville, VA
| | - Calvin X Geng
- Department of Medicine, School of Medicine, University of Virginia, Charlottesville, VA
| | - Zachary H Henry
- Division of Gastroenterology & Hepatology, School of Medicine, University of Virginia, Charlottesville, VA
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Matchett CL, Simonetto DA, Kamath PS. Renal Insufficiency in Patients with Cirrhosis. Clin Liver Dis 2023; 27:57-70. [PMID: 36400467 DOI: 10.1016/j.cld.2022.08.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Renal failure is one of the most prevalent complications in patients with cirrhosis and is of the utmost prognostic relevance. Acute kidney injury (AKI) in cirrhosis results from a spectrum of etiologies, of which hepatorenal syndrome (HRS) carries the worst prognosis. Correct differentiation of the etiology of AKI in cirrhosis is imperative, as treatment defers substantially. This review summarizes the current diagnostic criteria, pathophysiology, diagnosis, and therapeutic concepts for AKI and HRS-AKI in cirrhosis.
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Affiliation(s)
- Caroline L Matchett
- Internal Medicine Residency Program, Department of Medicine, Mayo Clinic, 200 1st Street Southwest, Rochester, 55902 MN, USA
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, 200 1st Street Southwest, Rochester, 55902 MN, USA
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, 200 1st Street Southwest, Rochester, 55902 MN, USA.
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Wentworth BJ, Henry ZH, Siragy HM. How I Approach It: Adrenal Insufficiency in Cirrhosis. Am J Gastroenterol 2022; 117:1889-1893. [PMID: 35980083 PMCID: PMC9722576 DOI: 10.14309/ajg.0000000000001939] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 07/29/2022] [Indexed: 01/30/2023]
Affiliation(s)
- Brian J Wentworth
- Division of Gastroenterology & Hepatology, School of Medicine, University of Virginia, Charlottesville, VA
| | - Zachary H Henry
- Division of Gastroenterology & Hepatology, School of Medicine, University of Virginia, Charlottesville, VA
| | - Helmy M Siragy
- Division of Endocrinology & Metabolism, School of Medicine, University of Virginia, Charlottesville, VA
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Abstract
Hypothalamus-pituitary-adrenal axis assessment in patients with cirrhosis is challenging. The phenotype of fatigue, hypotension, electrolyte disarray, and abdominal pain characterizing primary adrenal insufficiency (AI) overlaps significantly with decompensated liver disease. Reliance on total cortisol assays in hypoproteinemic states is problematic, yet abnormal stimulated levels in cirrhosis are associated with poor clinical outcomes. Alternative measures including free plasma or salivary cortisol levels have theoretical merit but are limited by unclear prognostic significance and undefined cirrhosis-specific reference ranges. Further complicating matters is that AI in cirrhosis represents a spectrum of impairment. Although absolute cortisol deficiency can occur, this represents a minority of cases. Instead, there is an emerging concept that cirrhosis, with or without critical illness, may induce a “relative” cortisol deficiency during times of stress. In addition, the limitations posed by decreased synthesis of binding globulins in cirrhosis necessitate re-evaluation of traditional AI diagnostic thresholds.
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Affiliation(s)
- Brian J Wentworth
- Division of Gastroenterology & Hepatology, School of Medicine, University of Virginia , Charlottesville, VA
| | - Helmy M Siragy
- Division of Endocrinology & Metabolism, School of Medicine, University of Virginia , Charlottesville, VA
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11
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Assessment of adrenal response in patients with stable cirrhosis and ascites using different short Synacthen tests and definitions. Eur J Gastroenterol Hepatol 2021; 33:e540-e547. [PMID: 33905212 DOI: 10.1097/meg.0000000000002153] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND AND AIMS The definition of relative adrenal insufficiency (RAI) in patients with cirrhosis remains controversial. We investigated the serum and salivary cortisol (SalC) response after low-dose and standard-dose Synacthen test in patients with stable cirrhosis and ascites. METHODS Ninety-five cirrhotic patients with ascites were prospectively evaluated from January 2014 to January 2018. Low-dose [adrenocorticotrophic hormone (ACTH): 1 μg] and standard-dose (ACTH: 250 μg) Synacthen test were successively performed. Paired serum total and saliva cortisol were taken at baseline, 30 min (low-dose test) and 60 min (standard-dose test). Salivary and Δserum total cortisol criteria included post-ACTH SalC < 12.7 ng/ml and/or SalC increase <3 ng/ml and serum total cortisol increase <9 μg/dl, respectively. RESULTS The prevalence of RAI varied according to the definition used. SalC-defined RAI was significantly more common after low-dose than standard-dose test (54.7% vs. 20%; P < 0.001). Δserum total cortisol-defined RAI was also significantly more frequent after low-dose than standard-dose test (66.3% vs. 24.2%; P < 0.001). Considering low-dose test/SalC criteria as reference diagnostic criteria, standard-dose/salivary and Δserum total cortisol criteria showed low specificity for RAI diagnosis (43.9% and 52.7%, respectively). Survival probability was significantly lower in patients with low-dose test/SalC-defined RAI compared to those without (53.8% vs. 79.1%; P = 0.01). SalC-defined RAI after low-dose test was significantly more common than that defined after standard-dose test (72.7% vs. 30.3%; P < 0.001) among patients who died. CONCLUSION Low-dose test/SalC definition can identify RAI in about half of patients with stable cirrhosis and ascites and is associated with increased mortality.
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Zhang J, Li J, Ding M, Chen Y, Duan Z. Cortisol in Peripheral Blood Predicts the Severity and Prognosis in Patients with Liver Failure at 90 Days. Risk Manag Healthc Policy 2021; 14:4311-4319. [PMID: 34703342 PMCID: PMC8528544 DOI: 10.2147/rmhp.s327440] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 09/23/2021] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE To investigate the cortisol level in peripheral blood in evaluating the severity and prognosis of patients with liver failure. METHODS A total of 211 inpatients with liver failure were enrolled in Beijing You 'an Hospital affiliated with Capital Medical University, from September 2018 to January 2020. They were divided into three groups according to the severity of liver failure: early-stage liver failure, medium-stage liver failure and end-stage liver failure. In all patients, peripheral venous blood was gathered to detect the level of peripheral cortisol and related biochemical indexes. Logistic regression was used to screen the risk factors affecting the prognosis of patients at 90 days. A receiver operating curve (ROC) was used to reflect the value of cortisol on the prognosis of patients at 90 days. A model for end-stage liver disease (MELD) was accessed. RESULTS Among these 211 patients with liver failure, aged from 19 to 70 years, the average level of cortisol was 351.26 ± 129.78 nmol/L for 101 cases with early-stage liver failure, 281.05 ± 81.31 nmol/L for 58 cases with medium-stage liver failure, and 189.21 ± 89.27 nmol/L for 52 cases with end-stage liver failure (P < 0.05). The level of cortisol in the survival group and the non-survival group was 339.26 ± 121.19 nmol/L and 192.71 ± 67.23 nmol/L, respectively (P < 0.05). The results of logistics regression analysis showed that the odds ratio (OR) and 95% confidence intervals (CI) of cortisol were 1.025 and 1.013-1.038 nmol/L (P < 0.05). MELD results showed that patients with higher MELD scores had lower cortisol content. CONCLUSION The level of cortisol is correlated with the severity of liver failure and decreases with the aggravation of liver failure, suggesting that the level of cortisol could be used as one of the indicators to evaluate the prognosis in patients with liver failure at 90 days.
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Affiliation(s)
- Jian Zhang
- Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China
| | - Junfeng Li
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, People’s Republic of China
| | - Mei Ding
- Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China
| | - Yu Chen
- Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China
| | - Zhongping Duan
- Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China
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Wentworth BJ, Haug RM, Northup PG, Caldwell SH, Henry ZH. Abnormal cholesterol metabolism underlies relative adrenal insufficiency in decompensated cirrhosis. Liver Int 2021; 41:1913-1921. [PMID: 34028160 DOI: 10.1111/liv.14970] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 05/02/2021] [Accepted: 05/18/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Relative adrenal insufficiency (RAI) in patients with cirrhosis is associated with increased mortality. Although the pathogenesis of RAI remains unclear, disordered cholesterol metabolism may contribute. METHODS We performed a prospective cohort study of 96 non-critically ill subjects with decompensated cirrhosis at a tertiary care centre. Subjects were administered 250 µcg cosyntropin, with RAI defined as an increase in total cortisol <9 µg/dL. High-density lipoprotein (HDL) levels and serum cholesterol esterification percentage (%CE), a validated surrogate marker of lecithin-cholesterol acyltransferase (LCAT) activity, were measured to assess the relationship between disordered cholesterol metabolism and the presence of RAI. Subjects were followed until death, liver transplantation or a maximum of 6 months. RESULTS Subjects with RAI had decreased levels of HDL (18 vs 29 mg/dL, P < .01) and %CE (64% vs 66%, P = .03). Correlation was seen between HDL and %CE (r = 0.7, R2 = 0.49; P < .01) and each integer decrease in %CE predicted an approximately 2% increase in the probability of RAI. Transplant-free survival was reduced in subjects with RAI at both 6 months (43% vs 71%, P = .01) and 90 days (54% vs 81%, P < .01). CONCLUSIONS Disruption in cholesterol metabolism contributes to the development of RAI in cirrhosis, as decreased LCAT activity leads to reduced HDL trafficking to the adrenal gland.
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Affiliation(s)
- Brian J Wentworth
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA
| | - Rebecca M Haug
- Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA
| | - Patrick G Northup
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA
| | - Stephen H Caldwell
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA
| | - Zachary H Henry
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA
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Piano S, Tonon M, Angeli P. Changes in the epidemiology and management of bacterial infections in cirrhosis. Clin Mol Hepatol 2021; 27:437-445. [PMID: 33504138 PMCID: PMC8273641 DOI: 10.3350/cmh.2020.0329] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/07/2021] [Accepted: 01/25/2021] [Indexed: 12/15/2022] Open
Abstract
Patients with cirrhosis are susceptible to develop infections because of immune dysfunction, changes in microbiome and increase in bacterial translocation from the gut to systemic circulation. Bacterial infections can worse the clinical course of the disease, triggering the development of complications such as acute kidney injury, hepatic encephalopathy, organ failures and acute on chronic liver failure. In recent years, the spread of multi drug resistant bacteria made more challenging the management of infections in patients with cirrhosis. Hence, the mortality rate associated to sepsis is increasing in these patients. Therefore, the optimization of the management of infections has a high priority in cirrhosis. Herein we reviewed the recent changes in the epidemiology and the management of bacterial infections in patients with liver cirrhosis.
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Affiliation(s)
- Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Marta Tonon
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
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Simbrunner B, Trauner M, Reiberger T, Mandorfer M. Recent advances in the understanding and management of hepatorenal syndrome. Fac Rev 2021; 10:48. [PMID: 34131658 PMCID: PMC8170686 DOI: 10.12703/r/10-48] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Renal dysfunction occurs frequently in hospitalized patients with advanced chronic liver disease (ACLD)/cirrhosis and has profound prognostic implications. In ACLD patients with ascites, hepatorenal syndrome (HRS) may result from circulatory dysfunction that leads to reduced kidney perfusion and glomerular filtration rate (in the absence of structural kidney damage). The traditional subclassification of HRS has recently been replaced by acute kidney injury (AKI) type of HRS (HRS-AKI) and non-AKI type of HRS (HRS-NAKI), replacing the terms “HRS type 1” and “HRS type 2”, respectively. Importantly, the concept of absolute serum creatinine (sCr) cutoffs for diagnosing HRS was partly abandoned and short term sCr dynamics now may suffice for AKI diagnosis, which facilitates early treatment initiation that may prevent the progression to HRS-AKI or increase the chances of AKI/HRS-AKI reversal. Recent randomized controlled trials have established (a) the efficacy of (long-term) albumin in the prevention of complications of ascites (including HRS-AKI), (b) the benefits of transjugular intrahepatic portosystemic shunt placement in patients with recurrent ascites, and (c) the superiority of terlipressin over noradrenaline for the treatment of HRS-AKI in the context of acute-on-chronic liver failure. This review article aims to summarize recent advances in the understanding and management of HRS.
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Affiliation(s)
- Benedikt Simbrunner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
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Zhang J, Li J, Chen Y, Ding M, Duan Z. Prognostic Factors Related to the Mortality Rate of Acute-on-Chronic Liver Failure Patients. Diabetes Metab Syndr Obes 2021; 14:2573-2580. [PMID: 34135609 PMCID: PMC8200164 DOI: 10.2147/dmso.s309641] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 04/21/2021] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Critical illness-related corticosteroid insufficiency (CIRCI) is known to be a common complication in patients with acute-on-chronic liver failure (ACLF). However, factors that predict the survival rate of ACLF patients remain unclear. The present study aims to determine the prognostic factors that impinge on the survival rate of ACLF patients. METHODS A total of 90 patients with ACLF at different stages, with or without CIRCI, were prospectively evaluated. RESULTS Various clinical factors were found to be significantly different among patients at early, mid and late stages of ACLF, as well as between the same population of patients with and without CIRCI. Specifically, patients at later stages of ACLF and patients with CIRCI had significantly higher Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD) and ACLF Research Consortium (AARC)-ACLF scores. CIRCI was observed in 20% of the enrolled patients (18 out of 90). In addition, the 90-day mortality rate was higher in mid- and late-stage ACLF patients, as well as patients with CIRCI. CONCLUSION ACLF stage and CIRCI predict early mortality in patients with ACLF and could be actively monitored in these patients for prioritized liver transplantation.
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Affiliation(s)
- Jian Zhang
- Difficult & Complicated Liver diseases and Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China
- Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, People’s Republic of China
| | - Junfeng Li
- The First Hospital of Lanzhou University, Department of Infectious Diseases, Lanzhou, People’s Republic of China
| | - Yu Chen
- Difficult & Complicated Liver diseases and Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China
- Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, People’s Republic of China
| | - Mei Ding
- Difficult & Complicated Liver diseases and Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China
- Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, People’s Republic of China
| | - Zhongping Duan
- Difficult & Complicated Liver diseases and Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China
- Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, People’s Republic of China
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Abstract
Hepatorenal syndrome (HRS), the extreme manifestation of renal impairment in patients with cirrhosis, is characterized by reduction in renal blood flow and glomerular filtration rate. Hepatorenal syndrome is diagnosed when kidney function is reduced but evidence of intrinsic kidney disease, such as hematuria, proteinuria, or abnormal kidney ultrasonography, is absent. Unlike other causes of acute kidney injury (AKI), hepatorenal syndrome results from functional changes in the renal circulation and is potentially reversible with liver transplantation or vasoconstrictor drugs. Two forms of hepatorenal syndrome are recognized depending on the acuity and progression of kidney injury. The first represents an acute impairment of kidney function, HRS-AKI, whereas the second represents a more chronic kidney dysfunction, HRS-CKD (chronic kidney disease). In this review, we provide critical insight into the definition, pathophysiology, diagnosis, and management of hepatorenal syndrome.
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Affiliation(s)
- Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA
| | - Pere Gines
- Liver Unit, Hospital Clinic, University of Barcelona IDIBAPS - CIBEReHD, Barcelona, Spain
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA
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Piano S, Favaretto E, Tonon M, Antonelli G, Brocca A, Sticca A, Mareso S, Gringeri E, Scaroni C, Plebani M, Russo FP, Burra P, Cillo U, Angeli P. Including Relative Adrenal Insufficiency in Definition and Classification of Acute-on-Chronic Liver Failure. Clin Gastroenterol Hepatol 2020; 18:1188-1196.e3. [PMID: 31589973 DOI: 10.1016/j.cgh.2019.09.035] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 09/14/2019] [Accepted: 09/26/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Relative adrenal insufficiency (RAI) is defined by insufficient production of cortisol relative to organ demand. RAI is observed frequently in hospitalized patients with cirrhosis, but there is disagreement over the clinical effects of RAI in these patients. We evaluated the prevalence and the clinical effects of RAI in hospitalized patients with cirrhosis. METHODS We performed a prospective study of 160 patients admitted to a hospital in Italy for acute decompensation of cirrhosis from May 2011 through September 2016. Patients were followed up until death, liver transplantation, or a maximum of 90 days. Serum and salivary levels of cortisol were measured before and after a 1-hour Short Synacthen Test. A diagnosis of RAI was given to patients with an increase in serum cortisol of less than 9 μg/dL, after Synacthen administration, in patients with baseline serum levels of cortisol less than 35 μg/dL. We collected blood samples before the Synacthen test and analyzed them for blood cell counts, liver and renal function, levels of C-reactive protein, and lipid profiles (total cholesterol, high-density lipoprotein cholesterol, apolipoprotein-A1). RESULTS A diagnosis of RAI was made for 78 patients (49%). Age (odds ratio [OR], 0.95; P = .030), number of leukocytes (OR, 3.10; P = .006), and levels of high-density lipoprotein cholesterol (OR, 0.30; P = .039) were associated independently with RAI. Patients with RAI had a significantly higher risk of developing bacterial infections (hazard ratio [HR], 1.60; P = .038), sepsis (HR, 2.95; P = .001), septic shock (HR, 4.94; P = .038), new organ failures (HR, 2.45; P = .014), and acute-on-chronic liver failure (HR, 2.27; P = .037) than patients without RAI. RAI was associated independently with death within 90 days of diagnosis (subdistribution HR, 4.83; P = .001). Patients with RAI and mild renal dysfunction or hepatic encephalopathy had no significant difference in cumulative incidence of 28-day mortality vs patients with acute-on-chronic liver failure grade 1 (25% vs 22%). CONCLUSIONS We found RAI to occur in almost half of patients admitted to a hospital for acute decompensation of cirrhosis. RAI was associated with a deficit of substrates for steroidogenesis and an increase in markers of inflammation. Patients with RAI have a high risk of developing sepsis, septic shock, organ failure, and death within 90 days. RAI has similar prognostic value to nonrenal organ failures.
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Affiliation(s)
- Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Elisa Favaretto
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Marta Tonon
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Giorgia Antonelli
- Unit of Laboratory Medicine, Department of Medicine, University of Padova, Padova, Italy
| | - Alessandra Brocca
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Antonietta Sticca
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Sara Mareso
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Carla Scaroni
- Unit of Endocrinology, Department of Medicine, University of Padova, Padova, Italy
| | - Mario Plebani
- Unit of Laboratory Medicine, Department of Medicine, University of Padova, Padova, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy.
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Nandish HK, Arun CS, Nair HR, Gopalakrishna R, Kumar H, Venu RP. Adrenal insufficiency in decompensated cirrhotic patients without infection: prevalence, predictors and impact on mortality. J R Coll Physicians Edinb 2019; 49:277-281. [PMID: 31808452 DOI: 10.4997/jrcpe.2019.405] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Relative adrenal insufficiency (RAI) is common in compensated and decompensated chronic liver disease in the presence of sepsis. This study was performed to find out the prevalence of RAI in decompensated cirrhotic patients presenting with hepatic encephalopathy and variceal bleeding without any evidence of infection. METHODS The study prospectively included 75 cirrhotic patients with signs of decompensation. The short Synacthen test (SST) was performed on all patients after ruling out infection. Patients with positive blood, urine, sputum, ascitic and pleural fluid cultures or evidence of infection on chest X-ray and those with elevated procalcitonin levels (>0.05 ng/ml) were excluded. RAI in critical illness was defined by a delta cortisol level (difference between basal and post-stimulation cortisol) of ≤9 μg/dl after SST. RESULTS The mean age of the study population was 54 ± 11 years. Upper gastrointestinal bleed and hepatic encephalopathy were seen in 56.6% and 41.5%, respectively, and both were seen in 1.9%. Of the 75 patients, 55 (73%) were in Child-Turcotte-Pugh (CTP) class C and the mean model for end-stage liver disease (MELD) score was 21 ± 7. Forty-five patients (60%) met our criteria for RAI. Those with RAI had lower serum albumin (2.4 ± 0.5 g/dl vs 2.7 ± 0.5 g/dl, p = 0.03) and higher MELD scores (22 ± 7 vs 19 ± 6, p = 0.03). Prevalence of RAI in CTP class C was 65% (36 out of 55 patients) compared to 45% (9 out of 20 patients) in Child-Pugh stage A and B. Similarly, 82% (23 out of 28 patients) with MELD scores >25 had RAI compared to 54% with MELD scores <20. None of biochemical parameters were predictive of RAI on logistic regression analysis. Three-month mortality rate was not significantly different in patients with or without adrenal insufficiency (44% vs 28%, p = 0.11). CONCLUSION The present study showed RAI to be common in noninfected decompensated cirrhotic patients, but did not predict 3-month mortality. There were no other predictive factors in those with RAI. Hence, in patients with cirrhosis without infection, the clinical utility of routine adrenal function testing needs further elucidation.
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Affiliation(s)
- Hullenahalli K Nandish
- Centre for Liver Diseases, Digestive Diseases Institute, Amrita Institute of Medical Sciences, Kerala, India
| | - Chankramath S Arun
- Department of Endocrinology, Amrita Institute of Medical Sciences, Ponekkara, Kochi-41, India,
| | - Harikumar R Nair
- Centre for Liver Diseases, Digestive Diseases Institute, Amrita Institute of Medical Sciences, Kerala, India
| | - Rajesh Gopalakrishna
- Centre for Liver Diseases, Digestive Diseases Institute, Amrita Institute of Medical Sciences, Kerala, India
| | - Harish Kumar
- Department of Endocrinology and Metabolism, Amrita Institute of Medical Sciences, Kerala, India
| | - Rama P Venu
- Centre for Liver Diseases, Digestive Diseases Institute, Amrita Institute of Medical Sciences, Kerala, India
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Angeli P, Bernardi M, Villanueva C, Francoz C, Mookerjee RP, Trebicka J, Krag A, Laleman W, Gines P. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol 2018; 69:406-460. [PMID: 29653741 DOI: 10.1016/j.jhep.2018.03.024] [Citation(s) in RCA: 1759] [Impact Index Per Article: 251.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 03/28/2018] [Indexed: 02/06/2023]
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Park SH, Joo MS, Kim BH, Yoo HN, Kim SE, Kim JB, Jang MK, Kim DJ, Lee MS. Clinical characteristics and prevalence of adrenal insufficiency in hemodynamically stable patients with cirrhosis. Medicine (Baltimore) 2018; 97:e11046. [PMID: 29952944 PMCID: PMC6039635 DOI: 10.1097/md.0000000000011046] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2017] [Accepted: 05/13/2018] [Indexed: 01/15/2023] Open
Abstract
It is well known that adrenal insufficiency is common in septic shock or hemodynamically unstable patients. But, there is as yet no sufficient clinically significant data about the exact prevalence or differences in the cause of cirrhosis with adrenal insufficiency. To investigate adrenal insufficiency prevalence in hemodynamically stable patients with cirrhosis and determine differences based on cirrhosis severity or etiology.From July 2011 to December 2012, 69 hemodynamically stable patients with cirrhosis without infection admitted at Hallym University Medical Center were enrolled. Adrenal insufficiency was defined as a peak cortisol level < 18 μg/dL, 30 or 60 minutes after 250 μg Synacthen injection.The study included 55 male patients (79.7%), and the mean age was 57.9 ± 12.9 years. Cirrhosis etiology was alcohol consumption, HBV, HCV, both viral and alcohol related, and cryptogenic in 49, 15, 7, 11, 9 patients, respectively. Adrenal insufficiency occurred in 24 patients (34.8%). No differences were found in age, sex, mean arterial pressure, heart rate, HDL, cirrhosis etiology, degree of alcohol consumption, encephalopathy, variceal bleeding history, or hepatocellular carcinoma between patients with or without adrenal insufficiency. Serum albumin level was lower (P < .05), and INR was higher (P < .05) in patients with than in those without adrenal insufficiency. However, multivariate analysis revealed no independent adrenal insufficiency predictor. Significant negative correlations were found between Child-Pugh score and peak cortisol levels (γ=-0.365, P = .008).Adrenal insufficiency was frequent even in hemodynamically stable patients with cirrhosis and tended to be associated with only liver disease severity, being unrelated to cirrhosis etiology.
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Relative Adrenal Insufficiency in Patients with Cirrhosis: A Systematic Review and Meta-Analysis. Dig Dis Sci 2017; 62:1067-1079. [PMID: 28176190 DOI: 10.1007/s10620-017-4471-8] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2016] [Accepted: 01/20/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Relative adrenal insufficiency (RAI) is frequently observed in patients with cirrhosis. We sought to identify evidence in the literature regarding the impact of RAI on clinical outcomes in cirrhotic patients. METHODS We conducted a systematic review (SR) and meta-analysis (MA) using the Ovid-MEDLINE, EMBASE, and Cochrane Library databases to identify relevant studies in the literature. RESULTS Of the 182 studies identified, 16 were eligible according to our inclusion criteria. The prevalence of RAI was 49.4% (744/1507), and cirrhotic patients with acute critical illnesses such as sepsis were more likely to have RAI compared to those without critical illnesses (P < 0.001). With respect to clinical outcomes, patients with RAI had poorer survival rates and an increased risk of complications such as bleeding and hepatorenal syndrome compared to those without RAI. Corticosteroid therapy had a beneficial effect on critically ill cirrhotic patients in terms of hospital survival rate. CONCLUSIONS Based on this SR and MA, critically ill patients with cirrhosis have a high risk of RAI, and the presence of RAI is related to a poor prognosis and occurrence of cirrhotic complications.
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Endogenous glucocorticoids exacerbate cholestasis-associated liver injury and hypercholesterolemia in mice. Toxicol Appl Pharmacol 2016; 306:1-7. [DOI: 10.1016/j.taap.2016.06.031] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Revised: 06/27/2016] [Accepted: 06/29/2016] [Indexed: 01/19/2023]
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Chiriac Ş, Stanciu C, Negru R, Trifan A. ASSESSMENT OF ADRENOCORTICAL DYSFUNCTION IN PATIENTS WITH STABLE LIVER CIRRHOSIS. ACTA ENDOCRINOLOGICA (BUCHAREST, ROMANIA : 2005) 2016; 12:262-267. [PMID: 31149099 PMCID: PMC6535276 DOI: 10.4183/aeb.2016.262] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
INTRODUCTION Relative adrenal insufficiency (RAI) is common in the setting of critical illness as well as in hemodynamically instable cirrhotic patients with sepsis. Several studies have also shown that RAI is frequent in patients with stable cirrhosis without sepsis. The aim of this study was to prospectively assess the incidence of RAI in patients with stable cirrhosis. PATIENTS AND METHODS Forty-seven patients with hemodynamically stable liver cirrhosis without sepsis were prospectively included. RAI, assessed by using low dose-short Synacthen test (LD-SST), was defined as either a basal total cortisol concentration below 3.6 µg/dL or a peak total serum cortisol ≤ 16 µg/dL at 30 min after stimulation. RESULTS RAI was present in 10 (21.3%) of 47 cirrhotic patients. Peak cortisol level was negatively correlated with the severity of cirrhosis evaluated by Child-Turcotte-Pugh (CTP) (r=-0.46; P=0.001) and Model for End-Stage Liver Disease (MELD) (r=-0.51; P=0.001) scores. The frequency of RAI increased from CTP-A (10%) to CTP-B (30%) to CTP-C (60%). CONCLUSION RAI diagnosed by LD-SST is frequent in patients with stable cirrhosis and is related to the severity of liver disease. Further studies are needed to define clinical importance of RAI in stable cirrhotic patients.
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Affiliation(s)
- Ş. Chiriac
- “Grigore T. Popa” University of Medicine and Pharmacy, Iaşi, Romania
| | - C. Stanciu
- “St. Spiridon” Emergency Hospital - Institute of Gastroenterology and Hepatology, Iaşi, Romania
| | - R. Negru
- “Grigore T. Popa” University of Medicine and Pharmacy, Iaşi, Romania
| | - A. Trifan
- “Grigore T. Popa” University of Medicine and Pharmacy, Iaşi, Romania
- “St. Spiridon” Emergency Hospital - Institute of Gastroenterology and Hepatology, Iaşi, Romania
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