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Item Activated recombinant factor VIIa should not be used in patients with refractory variceal bleeding: it is mostly ineffective, is expensive, and may rarely cause serious adverse events(Wiley Blackwell (John Wiley & Sons), 2014-11) Sozio, Margaret S.; Chalasani, Naga; Department of Medicine, IU School of MedicineItem Attacking Alcohol-Related Liver Disease by Taxing Alcohol Sales(Wiley, 2021) Tapper, Elliot B.; Parikh, Neehar D.; Liangpunsakul, Suthat; Medicine, School of MedicineItem Changing epidemiology and outcomes of acute kidney injury in hospitalized patients with cirrhosis - a US population-based study(Elsevier, 2020-11) Desai, Archita P.; Knapp, Shannon M.; Orman, Eric S.; Ghabril, Marwan S.; Nephew, Lauren D.; Anderson, Melissa; Ginès, Pere; Chalasani, Naga P.; Patidar, Kavish R.; Medicine, School of MedicineBackground & aims: Acute kidney injury (AKI) is a significant clinical event in cirrhosis yet contemporary population-based studies on the impact of AKI on hospitalized cirrhotics are lacking. We aimed to characterize longitudinal trends in incidence, healthcare burden and outcomes of hospitalized cirrhotics with and without AKI using a nationally representative dataset. Methods: Using the 2004-2016 National Inpatient Sample (NIS), admissions for cirrhosis with and without AKI were identified using ICD-9 and ICD-10 codes. Regression analysis was used to analyze the trends in hospitalizations, costs, length of stay and inpatient mortality. Descriptive statistics, simple and multivariable logistic regression were used to assess associations between individual characteristics, comorbidities, and cirrhosis complications with AKI and death. Results: In over 3.6 million admissions for cirrhosis, 22% had AKI. AKI admissions were more costly (median $13,127 [IQR $7,367-$24,891] vs. $8,079 [IQR $4,956-$13,693]) and longer (median 6 [IQR 3-11] days vs. 4 [IQR 2-7] days). Over time, AKI prevalence doubled from 15% in 2004 to 30% in 2016. CKD was independently and strongly associated with AKI (adjusted odds ratio 3.75; 95% CI 3.72-3.77). Importantly, AKI admissions were 3.75 times more likely to result in death (adjusted odds ratio 3.75; 95% CI 3.71-3.79) and presence of AKI increased risk of mortality in key subgroups of cirrhosis, such as those with infections and portal hypertension-related complications. Conclusions: The prevalence of AKI is significantly increased among hospitalized cirrhotics. AKI substantially increases the healthcare burden associated with cirrhosis. Despite advances in cirrhosis care, a significant gap remains in outcomes between cirrhotics with and without AKI, suggesting that AKI continues to represent a major clinical challenge.Item Comparison of clinical prediction rules for ruling out cirrhosis in nonalcoholic fatty liver disease (NAFLD)(Wiley, 2022) Brandman, Danielle; Boyle, Marie; McPherson, Stuart; Van Natta, Mark L.; Sanyal, Arun J.; Kowdley, Kris; Neuschwander-Tetri, Brent; Chalasani, Naga; Abdelmalek, Manal F.; Terrault, Norah A.; McCullough, Art; Bettencourt, Ricki; Caussy, Cyrielle; Kleiner, David E.; Behling, Cynthia; Tonascia, James; Anstee, Quentin M.; Loomba, Rohit; Members of the Nonalcoholic Steatohepatitis Clinical Research Network; Medicine, School of MedicineBackground and aims: Patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis benefit from referral to subspecialty care. While several clinical prediction rules exist to identify advanced fibrosis, the cutoff for excluding cirrhosis due to NAFLD is unclear. This analysis compared clinical prediction rules for excluding biopsy-proven cirrhosis in NAFLD. Methods: Adult patients were enrolled in the NASH Clinical Research Network (US) and the Newcastle Cohort (UK). Clinical and laboratory data were collected at enrolment, and a liver biopsy was taken within 1 year of enrolment. Optimal cutoffs for each score (eg, FIB-4) to exclude cirrhosis were derived from the US cohort, and sensitivity, specificity, positive predictive value, negative predictive value and AUROC were calculated. The cutoffs were evaluated in the UK cohort. Results: 147/1483 (10%) patients in the US cohort had cirrhosis. All prediction rules had similarly high NPV (0.95-0.97). FIB-4 and NAFLD fibrosis scores were the most accurate in characterising patients as having cirrhosis (AUROC 0.84-0.86). 59/494 (12%) patients in the UK cohort had cirrhosis. Prediction rules had high NPV (0.92-0.96), and FIB-4 and NAFLD fibrosis score the most accurate in the prediction of cirrhosis in the UK cohort (AUROC 0.87-0.89). Conclusions: This cross-sectional analysis of large, multicentre international datasets shows that current clinical prediction rules perform well in excluding cirrhosis with appropriately chosen cutoffs. These clinical prediction rules can be used in primary care to identify patients, particularly those who are white, female, and <65, unlikely to have cirrhosis so higher-risk patients maintain access to specialty care.Item CT and MRI imaging and interpretation of hepatic arterioportal shunts(AME Publishing Company, 2019-05-21) Wang, Qiushi; Koniaris, Leonidas G.; Milgrom, Daniel P.; Patel, Aash; Hu, Maoqing; Cui, Enming; Deng, Yu; Akisik, Fatih; Radiology and Imaging Sciences, School of MedicineHepatic arterioportal shunts (HAPS) occur due to organic or functional fistulization of blood flow between arterial hepatic vasculature and venous portal systems. It is a type of hemodynamic abnormality of the liver being observed increasingly with the use of temporal imaging modalities. HAPS occur due to other underlying hepatic abnormalities including the presence of an underlying tumor or malignancy. When a HAPS is present, the appearance of these abnormalities on imaging studies suggests an underlying abnormality, must be considered atypical even if asymptomatic, and warrants careful evaluation. Over time, and as a function of degree of fistulae, symptoms and potential life-threatening complications may arise from the HAPS. These systemic complications may include the development of portal hypertension, splenomegaly, as well as accelerated metastasis in patients with malignant tumors. This manuscript reviews common underlying conditions associated with HAPS and their radiologic interpretation.Item CT-scan Based Liver and Spleen Volume Measurement as a Prognostic Indicator for Patients with Cirrhosis(Elsevier, 2021-09) Patel, Milan; Tann, Mark; Liangpunsakul, Suthat; Radiology and Imaging Sciences, School of MedicineBackground: Complications of patients with liver disease generally occurs as the consequence of advanced fibrosis and portal hypertension. Non-invasive tools to predict the complications may allow for better risk-stratification and medical management in patients with cirrhosis. The goals of this study were to determine the utility of CT-scan based liver and spleen volume measurement in association with complications and outcomes in patients with cirrhosis. Methods: Baseline demographic and clinical characteristics of 556 patients with cirrhosis who underwent CT scan of the abdomen between January 1-June 30,2009 were reviewed. Liver and spleen volume were measured using semi-automated interactive software and compared to 47 healthy controls. The association between liver and spleen volume and complications of cirrhosis was determined. Independent predictors of survival were analyzed with Cox regression model. Results: Patients with cirrhosis had significantly lower total and functional liver volume, larger total and functional spleen volume, and significantly lower total liver to spleen volume ratio when compared to controls. Liver volume, spleen volume, and liver to spleen volume ratio were significantly altered in patients with decompensated stage. Patients with hepatic encephalopathy had significantly lower total liver volume and spleen size was associated with the presence of esophageal varices. Patients with cirrhosis who underwent liver transplantation had significantly lower total liver volume and larger total spleen volume. However, spleen volume was not an independent predictor for mortality. Conclusions: Baseline liver and spleen volume and its ratio are significantly altered in patients with cirrhosis. Spleen volume is also associated with the presence of esophageal varices.Item A dedicated paracentesis clinic decreases healthcare utilization for serial paracenteses in decompensated cirrhosis(Springer Nature, 2018-08) Cheng, Yao-Wen; Sandrasegaran, Kumar; Cheng, Katherine; Shah, Angela; Ghabril, Marwan; Berry, William; Lammert, Craig; Chalasani, Naga; Orman, Eric S.; Radiology and Imaging Sciences, School of MedicinePURPOSE: The purpose of the study is to describe the effect of a dedicated paracentesis clinic on healthcare utilization by patients with decompensated cirrhosis and refractory ascites. METHODS: This Institutional Review Board-approved retrospective study identified cirrhotic patients receiving paracenteses over a 6-month period before and after creating the paracentesis clinic. Patients were followed for 12 months to collect outcome data including characteristics of subsequent hospitalizations and paracenteses. Logistic regression was used to examine the association between the paracentesis clinic and outcomes. RESULTS: There were 183 patients and 1364 paracenteses performed during the study time period. Age, gender, cirrhosis etiology, MELD, Child-Pugh, and Charlson comorbidity index were comparable between the two groups. Rates of mortality, transplant, and hospitalization were also similar during 1 year follow-up. After establishment of the paracentesis clinic, median paracenteses per patient increased from 2 (IQR 1-7) to 4 (IQR 2-11) (P = 0.01); albumin replacement after paracenteses ≥ 5 L improved from 76.3% to 91.7% (P < 0.001); and the fraction of outpatient paracenteses performed in the emergency department decreased from 13.4% to 3.8% (P < 0.001). Major complications remained negligible at 0.81% across both time periods. While fewer patients were admitted for ascites after the paracentesis clinic (39.6% vs. 20.8%, P = 0.009), more patients had acute kidney injury (AKI) during follow-up (47.2% vs. 65.9%, P = 0.02), with a trend towards more AKI admissions (22.6% vs. 35.4%, P = 0.09). CONCLUSION: A dedicated paracentesis clinic can improve access and wait times, while also reducing admissions for ascites and paracenteses performed in the emergency department.Item Defining the serum proteomic signature of hepatic steatosis, inflammation, ballooning and fibrosis in non-alcoholic fatty liver disease(Elsevier, 2023) Sanyal, Arun J.; Williams, Stephen A.; Lavine, Joel E.; Neuschwander-Tetri, Brent A.; Alexander, Leigh; Ostroff, Rachel; Biegel, Hannah; Kowdley, Kris V.; Chalasani, Naga; Dasarathy, Srinivasan; Diehl, Anna Mae; Loomba, Rohit; Hameed, Bilal; Behling, Cynthia; Kleiner, David E.; Karpen, Saul J.; Williams, Jessica; Jia, Yi; Yates, Katherine P.; Tonascia, James; Medicine, School of MedicineBackground & aims: Despite recent progress, non-invasive tests for the diagnostic assessment and monitoring of non-alcoholic fatty liver disease (NAFLD) remain an unmet need. Herein, we aimed to identify diagnostic signatures of the key histological features of NAFLD. Methods: Using modified-aptamer proteomics, we assayed 5,220 proteins in each of 2,852 single serum samples from 636 individuals with histologically confirmed NAFLD. We developed and validated dichotomized protein-phenotype models to identify clinically relevant severities of steatosis (grade 0 vs. 1-3), hepatocellular ballooning (0 vs. 1 or 2), lobular inflammation (0-1 vs. 2-3) and fibrosis (stages 0-1 vs. 2-4). Results: The AUCs of the four protein models, based on 37 analytes (18 not previously linked to NAFLD), for the diagnosis of their respective components (at a clinically relevant severity) in training/paired validation sets were: fibrosis (AUC 0.92/0.85); steatosis (AUC 0.95/0.79), inflammation (AUC 0.83/0.72), and ballooning (AUC 0.87/0.83). An additional outcome, at-risk NASH, defined as steatohepatitis with NAFLD activity score ≥4 (with a score of at least 1 for each of its components) and fibrosis stage ≥2, was predicted by multiplying the outputs of each individual component model (AUC 0.93/0.85). We further evaluated their ability to detect change in histology following treatment with placebo, pioglitazone, vitamin E or obeticholic acid. Component model scores significantly improved in the active therapies vs. placebo, and differential effects of vitamin E, pioglitazone, and obeticholic acid were identified. Conclusions: Serum protein scanning identified signatures corresponding to the key components of liver biopsy in NAFLD. The models developed were sufficiently sensitive to characterize the longitudinal change for three different drug interventions. These data support continued validation of these proteomic models to enable a "liquid biopsy"-based assessment of NAFLD.Item Development and Validation of a Model to Predict Acute Kidney Injury in Hospitalized Patients With Cirrhosis(Wolters Kluwer, 2019-09) Patidar, Kavish R.; Xu, Chenjia; Shamseddeen, Hani; Cheng, Yao-Wen; Ghabril, Marwan S.; Mukthinuthalapati, V.V. Pavan K.; Fricker, Zachary P.; Akinyeye, Samuel; Nephew, Lauren D.; Desai, Archita P.; Anderson, Melissa; El-Achkar, Tarek M.; Chalasani, Naga P.; Orman, Eric S.; Medicine, School of MedicineOBJECTIVES: Acute kidney injury (AKI) is a common complication in hospitalized patients with cirrhosis which contributes to morbidity and mortality. Improved prediction of AKI in this population is needed for prevention and early intervention. We developed a model to identify hospitalized patients at risk for AKI. METHODS: Admission data from a prospective cohort of hospitalized patients with cirrhosis without AKI on admission (n = 397) was used for derivation. AKI development in the first week of admission was captured. Independent predictors of AKI on multivariate logistic regression were used to develop the prediction model. External validation was performed on a separate multicenter cohort (n = 308). RESULTS: In the derivation cohort, the mean age was 57 years, the Model for End-Stage Liver Disease score was 17, and 59 patients (15%) developed AKI after a median of 4 days. Admission creatinine (OR: 2.38 per 1 mg/dL increase [95% CI: 1.47-3.85]), international normalized ratio (OR: 1.92 per 1 unit increase [95% CI: 1.92-3.10]), and white blood cell count (OR: 1.09 per 1 × 10/L increase [95% CI: 1.04-1.15]) were independently associated with AKI. These variables were used to develop a prediction model (area underneath the receiver operator curve: 0.77 [95% CI: 0.70-0.83]). In the validation cohort (mean age of 53 years, Model for End-Stage Liver Disease score of 16, and AKI development of 13%), the area underneath the receiver operator curve for the model was 0.70 (95% CI: 0.61-0.78). DISCUSSION: A model consisting of admission creatinine, international normalized ratio, and white blood cell count can identify patients with cirrhosis at risk for in-hospital AKI development. On further validation, our model can be used to apply novel interventions to reduce the incidence of AKI among patients with cirrhosis who are hospitalized.Item Drug Hepatotoxicity: Environmental Factors(Elsevier, 2017-02) Stine, Jonathan G.; Chalasani, Naga; Medicine, School of MedicineDrug-induced liver injury presents as various forms of acute and chronic liver disease. There is wide geographic variation in the most commonly implicated agents. Smoking can induce cytochrome P450 enzymes but this does not necessarily translate into clinically relevant drug-induced liver injury. Excessive alcohol consumption is a clear risk factor for intrinsic hepatotoxicity from acetaminophen and may predispose to injury from antituberculosis medications. Understanding of the role of infection, proinflammatory states, disorders of coagulation, and the hepatic clock in predisposing patients to drug-induced liver injury is evolving. More study focusing specifically on environmental risk factors predisposing patients to drug-induced liver injury is needed.