Basal cortisol levels do not predict adrenal responsiveness in acute decompensated cirrhosis.

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 (ß = 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.

Relative adrenal insufficiency in the non-critically ill patient with cirrhosis: A systematic review and meta-analysis.

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.

Abnormal cholesterol metabolism underlies relative adrenal insufficiency in decompensated cirrhosis.

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.

How to Identify the Patient with Nonalcoholic Steatohepatitis Who Will Progress to Cirrhosis.

Non-alcoholic fatty liver disease (NAFLD) figures prominently into the clinical hepatology landscape. NAFLD represents a disease spectrum comprising simple steatosis, steatosis with elevated liver enzymes, and non-alcoholic steatohepatitis (NASH), the entity with clear potential for fibrosis progression. Risk factors associated with fibrosis progression in NASH include histologic findings of lobular inflammation and any fibrosis as well as clinical comorbidities that include type 2 diabetes, obesity, and metabolic syndrome. Liver biopsy remains the gold standard in evaluating NASH; however, noninvasive methods are accumulating evidence for a growing role in identifying patients at increased risk to develop NASH, fibrosis, and potentially cirrhosis.

Editorial: "Lean" NAFLD: Metabolic Obesity with Normal BMI Is It in the Genes?

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. "Lean" NAFLD represents a patient subpopulation with hepatic steatosis evident on imaging with normal BMI. This paper by Feldman and Eder et al. illustrates the mild but clear metabolic differences and genetic connections in Caucasian lean NAFLD patients compared with obese NAFLD and healthy controls. Their findings highlight key similarities of lean and obese NAFLD compared with lean healthy subjects. This paper characterizes "lean" NAFLD as a unique phenotype with specific genetic associations deserving of further investigation in the greater scheme of elucidating the pathophysiology of fatty liver.

Spontaneous bacterial peritonitis prevalence in pre-transplant patients and its effect on survival and graft loss post-transplant.

AIM: To investigate the incidence of spontaneous bacterial peritonitis (SBP) in pre-transplant patients and its effect on post transplant mortality and graft failure. METHODS: We conducted a retrospective cohort study of patient records from the organ procurement and transplant network data set. Patients were identified by the presence of SBP pre-transplant. Univariate post-transplant survival models were constructed using the Kaplan-Meier technique and multivariate models were constructed using the Cox proportional hazards model. Variables that affected post-transplant graft survival were identified in the SBP population. RESULTS: Forty-seven thousand eight hundred and eighty patient records were included in the analysis for both groups, and 1966 (4.11%) patients were identified in the data set as having pre-transplant SBP. Patients that had pre-transplant SBP had higher rates of graft loss from recurrent hepatitis C virus (HCV) (3.6% vs 2.0%, P < 0.0001), infections leading to graft loss (1.9% vs 1.3%, P = 0.02), primary non-function (4.3% vs 3.0%, P < 0.0001) and chronic rejection (1.1% vs 0.7%, P = 0.04). Kaplan-Meier survival analysis showed a statistically significant difference in all-cause survival in patients with a history of SBP vs those without (P < 0.0001). Pre-transplant history of SBP was independently predictive of mortality due to recurrent HCV (HR = 1.11, 95%CI: 1.02-1.21, P < 0.017) after liver transplantation. CONCLUSION: HCV patients prior to the advent of directing acting anti-viral agents had a higher incidence of pre-transplant SBP than other patients on the liver transplant wait list. SBP history pre-transplant resulted in a higher rate of graft loss due to recurrent HCV infection and chronic rejection.

Prophylactic anticoagulation for venous thromboembolism in hospitalized cirrhosis patients is not associated with high rates of gastrointestinal bleeding.

BACKGROUND: Hospitalized patients with cirrhosis are at risk to develop venous thromboembolism. Although current guidelines support the routine administration of thromboprophylaxis to hospitalized patients, there is limited data regarding the safety or efficacy of this practice in hospitalized cirrhosis patients. AIMS: We aimed to determine if administration of thromboprophylaxis was associated with increased complication rates for hospitalized cirrhosis patients. METHODS: Data were collected on patients admitted to the University of Virginia between 2007 and 2010. Study personnel systematically collected data on complications, including gastrointestinal bleed, venous thromboembolism and death directly from the medical record. RESULTS: A total of 235 patients (accounting for 355 discrete hospitalizations in which thromboprophylaxis was administered) met inclusion criteria accounting for 1660 person-days of thromboprophylaxis administered to patients. The mean age at admission was 58 (95% CI 57.1-59.2) years and 217 (61%) were male patients. The mean admission model for end-stage liver disease (MELD) score was 16.2 (95% CI 15.5-16.9). The mean hospital length of stay was 6.5 (95% CI 5.9-7.4) days. In patients who received thromboprophylaxis, the mean treatment length was 4.7 days (95% CI 4.2-5.2). There were nine gastrointestinal bleeding events (2.5% of admissions), five venous thromboembolisms (1.4% of admissions), two cases of heparin-induced thrombocytopenia (0.5% of admissions) and 14 deaths overall (3.9% of admissions). CONCLUSIONS: The use of thromboprophylaxis in hospitalized cirrhosis patients is not associated with high rates of gastrointestinal bleeding or death.

Editorial: Beta-blockers and the prevention of decompensation in cirrhosis: worth the trouble.

Non-selective beta-blockers have been a cornerstone of therapy for prevention of esophageal variceal bleeding in cirrhosis patients for more than two decades. When lowering the hepatic vein portal pressure gradient (HVPG) below 12 mm Hg or decreasing the pressure by 20% from baseline, these drugs are of proven benefit in reducing variceal bleeding and improving survival in this patient population. The recent work by Hendández-Gea et al., suggests that initiation of the beta-blocker nadolol in cirrhosis patients with high-risk varices can delay or prevent the first occurrence of clinically evident ascites. This finding comes with some caveats, however. The beneficial effect was only seen in patients who had an improvement by 10% or more from baseline HVPG pressure (only 51% of the treated patients in this study). This class of medications has some risk and tolerance issues, and many patients do not respond, even when the heart rate is optimally decreased. Despite this, the use of beta-blockers may be beneficial in the primary prevention of the formation of ascites and further decompensation of cirrhosis.

Bleeding after percutaneous endoscopic gastrostomy is linked to serotonin reuptake inhibitors, not aspirin or clopidogrel.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is an invasive procedure that can result in bleeding. Guidelines recommend discontinuing clopidogrel for 7 to 10 days, but not withholding aspirin, before PEG. Serotonin reuptake inhibitors (SRIs) have been associated with an increased risk of GI bleeding. OBJECTIVE: To determine whether there is an association between periprocedural aspirin, clopidogrel, or SRI use and bleeding in patients who underwent PEG tube placement. DESIGN: Retrospective cohort study. SETTING: Large quaternary-care academic medical center. PATIENTS: A total of 990 patients (525 men) with a median age of 69.8 years who underwent PEG from January 1999 to April 2009. INTERVENTIONS: PEG tube placement. MAIN OUTCOME MEASUREMENTS: GI bleeding. RESULTS: Sixteen patients (1.6%) had evidence of bleeding during the first 48 hours after PEG, and 12 patients (1.2%) had evidence of bleeding between 48 hours and 14 days after PEG. Thirty-six patients (3.6%) received high-dose aspirin (>325 mg), 27 patients (2.7%) received clopidogrel (75 mg), and 99 patients (10%) received an SRI before PEG. Twenty-four patients (2.4%) received high-dose aspirin, 25 patients (2.5%) received clopidogrel, and 130 patients (13.1%) received an SRI after PEG. Multivariate analysis demonstrated no association between periprocedural use of aspirin (at any dose) or clopidogrel and post-PEG bleeding. However, SRIs administered 24 hours or less before PEG were associated with a significantly higher odds of post-PEG bleeding (adjusted odds ratio 4.1; 95% CI, 1.1-13.4; P = .04). LIMITATIONS: Retrospective, single-center study with limited statistical power despite a relatively large cohort of patients. CONCLUSIONS: Use of aspirin or clopidogrel before or after PEG was not associated with procedure-related bleeding. SRI use in the 24 hours before PEG was associated with an increased risk of bleeding.

Meshed capillary vessels found on narrow-band imaging without optical magnification effectively identifies colorectal neoplasia: a North American validation of the Japanese experience.

BACKGROUND: The presence of meshed capillary (MC) vessels is highly sensitive (96%) and specific (92%) for diagnosing colorectal neoplasia on colonoscopy by using narrow-band imaging (NBI) with optical magnification, which is not available in North America. However, the efficacy of NBI to identify an MC pattern without optical magnification has not been determined. OBJECTIVE: To determine the diagnostic capabilities of NBI colonoscopy without optical magnification in differentiating neoplastic from non-neoplastic colorectal polyps by using the MC pattern. DESIGN: Retrospective comparison of prospectively collected colorectal polyp data. SETTING: Large, academic medical center. PATIENTS: This study involved 126 consecutive colorectal polyps (median size 3 mm) that were found in 52 patients (33 men) with a median age of 59.5 years. INTERVENTION: All lesions identified by white-light colonoscopy were prospectively diagnosed in real-time by using the MC pattern as determined on high-definition NBI, with 1.5x zoom but without true optical magnification, and then endoscopically excised. Surgical pathology was used as the criterion standard. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of identifying neoplastic polyps were calculated. RESULTS: NBI without optical magnification was found to have a sensitivity of 93%, specificity of 88%, positive predictive value of 90%, negative predictive value of 91%, and diagnostic accuracy of 91% when all polyp sizes were considered. For lesions < or =5 mm, sensitivity was 87%, specificity was 93%, positive predictive value was 89%, negative predictive value was 91%, and diagnostic accuracy was 90%. LIMITATIONS: Single-center, single-endoscopist experience. CONCLUSION: Use of the MC pattern on NBI colonoscopy without optical magnification effectively distinguishes neoplastic from non-neoplastic colorectal polyps. NBI colonoscopy without optical magnification for neoplastic polyp diagnosis appears to be comparable with NBI with optical magnification when the MC pattern is used. A large, prospective trial is needed for further validation.