IU Indianapolis ScholarWorks :: Browsing by Author "Ghabril, Marwan S."

Browsing by Author "Ghabril, Marwan S."

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Admission Factor V Predicts Transplant-Free Survival in Acute Liver Failure
(Springer, 2021) Patidar, Kavish R.; Davis, Brian C.; Slaven, James E.; Ghabril, Marwan S.; Kubal, Chandrashekhar A.; Lee, William M.; Stravitz, Richard T.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
Background and aims: Traditional laboratory markers are insensitive in distinguishing between patients with acute liver failure (ALF) who will require urgent liver transplantation (LT) from those who will recover spontaneously, particularly within 24 h of presentation. Coagulation factor-V (FV) may improve the accuracy of outcome prediction in ALF due to its predominant synthesis in the liver and short half-life in plasma. Methods: Patients enrolled in the ALF Study Group Registry from a single site had FV determined within 24 h of presentation (Derivation-Cohort). Area under the receiver operating characteristic curves (AUROC) dichotomized by ALF etiology [acetaminophen (APAP) or non-APAP] were constructed to evaluate the diagnostic performance of FV for transplant-free-survival (TFS). Multivariate logistic regression modeling was performed using FV and other clinical variables to predict TFS. Accuracy of FV and multivariable model were performed in a Validation-Cohort from a different site. Results: 90-patients (56% with APAP) were included in the Derivation-Cohort. Median FV was significantly higher in TFS versus those who died/LT (31% vs. 15%, respectively; p = 0.001). When dichotomized by etiology, AUROC for FV was 0.77 for APAP (cutoff, sensitivity, specificity 10.5%, 79%, 69%, respectively) and 0.77 for non-APAP (22%, 85%, 67%, respectively). When the optimal cutoffs for FV in the Derivation-Cohort were applied to the Validation-Cohort (N = 51; 59% with APAP), AUROC for FV was 0.75 for APAP (sensitivity/specificity 81/44) and 0.95 for non-APAP (sensitivity/specificity 90/73). In multivariate analyses, AUROC for FV model was 0.86 in the Derivation-Cohort and 0.90 in the Validation-Cohort. Conclusion: Admission FV may improve selection of patients who are likely to improve without LT.
Admission plasma uromodulin and the risk of acute kidney injury in hospitalized patients with cirrhosis: a pilot study
(American Physiological Society, 2019-10-01) Patidar, Kavish R.; Garimella, Pranav S.; Macedo, Etienne; Slaven, James E.; Ghabril, Marwan S.; Weber, Regina E.; Anderson, Melissa; Orman, Eric S.; Nephew, Lauren D.; Desai, Archita P.; Chalasani, Naga; El-Achkar, Tarek M.; Medicine, School of Medicine
Acute kidney injury (AKI) is a common complication in hospitalized patients with cirrhosis. Uromodulin, a protein uniquely produced by the kidney and released both in the urine and circulation, has been shown to regulate AKI and is linked to tubular reserve. Although low levels of urine uromodulin are associated with AKI after cardiac surgery, it is unclear whether circulating uromodulin can stratify the risk of AKI, particularly in a susceptible population such as hospitalized patients with cirrhosis. Thus, we investigated whether plasma uromodulin measured at the time of admission is associated with subsequent hospital-acquired AKI (defined by a rise in serum creatinine >0.3mg/dL within 48 h or ≥ 1.5 times baseline) in patients with cirrhosis. A total of 98 patients [mean age 54 yr, Model for Endstage Liver Disease Sodium (MELD-Na) score 19, and baseline creatinine of 0.95 mg/dL] were included, of which 13% (n = 13) developed AKI. Median uromodulin levels were significantly lower in patients who developed AKI compared with patients who did not (9.30 vs. 13.35 ng/mL, P = 0.02). After adjusting for age, sex, diabetes, hypertension, albumin, and MELD-Na score as covariates on multivariable logistic regression, uromodulin was independently associated with AKI [odd ratios of 1.19 (95% confidence interval 1.02, 1.37; P = 0.02)]. Lower uromodulin levels on admission are associated with increased odds of subsequent AKI in hospitalized patients with cirrhosis. Further studies are needed to better understand the role of uromodulin in the pathogenesis and as a predictive biomarker of AKI in this population. NEW & NOTEWORTHY In this study, we found that admission plasma uromodulin levels are significantly lower in patients who developed subsequent acute kidney injury (AKI) during their hospital stay compared with patients who did not. Additionally, uromodulin is independently associated with AKI development after adjusting for clinically relevant parameters such as age, sex, diabetes, hypertension, severity of cirrhosis, and kidney function. To our knowledge, this is the first study linking plasma uromodulin with AKI development in patients with cirrhosis.
CAD-LT score effectively predicts risk of significant coronary artery disease in liver transplant candidates
(Elsevier, 2021-07) Rachwan, Rayan Jo; Kutkut, Issa; Timsina, Lava R.; Chaaya, Rody G. Bou; El-Am, Edward A.; Sabra, Mohammad; Mshelbwala, Fakilahyel S.; Rahal, Mahmoud A.; Lacerda, Marco A.; Kubal, Chandrashekhar A.; Fridell, Jonathan A.; Ghabril, Marwan S.; Bourdillon, Patrick D.; Mangus, Richard S.; Surgery, School of Medicine
Background & Aims Patients with cirrhosis and significant coronary artery disease (CAD) are at risk of peri-liver transplantation (LT) cardiac events. The coronary artery disease in liver transplantation (CAD-LT) score and algorithm aim to predict the risk of significant CAD in LT candidates and guide pre-LT cardiac evaluation. Methods Patients who underwent pre-LT evaluation at Indiana University (2010-2019) were studied retrospectively. Stress echocardiography (SE) and cardiac catheterization (CATH) reports were reviewed. CATH was performed for predefined CAD risk factors, irrespective of normal SE. Significant CAD was defined as CAD requiring percutaneous or surgical intervention. A multivariate regression model was constructed to assess risk factors. Receiver-operating curve analysis was used to compute a point-based risk score and a stratified testing algorithm. Results A total of 1,771 pre-LT patients underwent cardiac evaluation, including results from 1,634 SE and 1,266 CATH assessments. Risk-adjusted predictors of significant CAD at CATH were older age (adjusted odds ratio 1.05; 95% CI 1.03–1.08), male sex (1.69; 1.16–2.50), diabetes (1.57; 1.12–2.22), hypertension (1.61; 1.14–2.28), tobacco use (pack years) (1.01; 1.00–1.02), family history of CAD (1.63; 1.16–2.28), and personal history of CAD (6.55; 4.33–9.90). The CAD-LT score stratified significant CAD risk as low (≤2%), intermediate (3% to 9%), and high (≥10%). Among patients who underwent CATH, a risk-based testing algorithm (low: no testing; intermediate: non-invasive testing vs. CATH; high: CATH) would have identified 97% of all significant CAD and potentially avoided unnecessary testing (669 SE [57%] and 561 CATH [44%]). Conclusions The CAD-LT score and algorithm (available at www.cad-lt.com) effectively stratify pre-LT risk for significant CAD. This may guide more targeted testing of candidates with fewer tests and faster time to waitlist. Lay summary The coronary artery disease in liver transplantation (CAD-LT) score and algorithm effectively stratify patients based on their risk of significant coronary artery disease. The CAD-LT algorithm can be used to guide a more targeted cardiac evaluation prior to liver transplantation.
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 Medicine
Background & 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.
Clinical presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements
(Wiley, 2017-04) Bonkovsky, Herbert L.; Kleiner, David E.; Gu, Jiezhun; Odin, Joseph A.; Russo, Mark W.; Navarro, Victor M.; Fontana, Robert J.; Ghabril, Marwan S.; Barnhart, Huiman; Hoofnagle, Jay H.; U.S. Drug Induced Liver Injury Network Investigators; Medicine, School of Medicine
Bile duct loss during the course of drug-induced liver injury is uncommon, but can be an indication of vanishing bile duct syndrome (VBDS). In this work, we assess the frequency, causes, clinical features, and outcomes of cases of drug-induced liver injury with histologically proven bile duct loss. All cases of drug-induced liver injury enrolled into a prospective database over a 10-year period that had undergone liver biopsies (n = 363) were scored for the presence of bile duct loss and assessed for clinical and laboratory features, causes, and outcomes. Twenty-six of the 363 patients (7%) with drug-, herbal-, or dietary-supplement-associated liver injury had bile duct loss on liver biopsy, which was moderate to severe (<50% of portal areas with bile ducts) in 14 and mild (50%-75%) in 12. The presenting clinical features of the 26 cases varied, but the most common clinical pattern was a severe cholestatic hepatitis. The implicated agents included amoxicillin/clavulanate (n = 3), temozolomide (n = 3), various herbal products (n = 3), azithromycin (n = 2), and 15 other medications or dietary supplements. Compared to those without, those with bile duct loss were more likely to develop chronic liver injury (94% vs. 47%), which was usually cholestatic and sometimes severe. Five patients died and 2 others underwent liver transplantation for progressive cholestasis despite treatment with corticosteroids and ursodiol. The most predictive factor of poor outcome was the degree of bile duct loss on liver biopsy. CONCLUSION: Bile duct loss during acute cholestatic hepatitis is an ominous early indicator of possible VBDS, for which at present there are no known means of prevention or therapy.
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 Medicine
OBJECTIVES: 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.
EUS-guided fine needle injection is superior to direct endoscopic injection of 2-octyl cyanoacrylate for the treatment of gastric variceal bleeding
(Springer, 2018) Bick, Benjamin L.; Al-Haddad, Mohammad; Liangpunsakul, Suthat; Ghabril, Marwan S.; DeWitt, John M.; Medicine, School of Medicine
Background Endoscopic injection of cyanoacrylate into gastric varices may be performed by EUS-guided fine needle injection (EUS-FNI) or direct endoscopic injection (DEI). The aim of this study is to compare the rate of recurrent GV bleeding and adverse events between DEI and EUS-FNI for treatment of GV. Methods In a single-center study, a retrospective cohort of patients with actively/recently bleeding or high-risk GV treated with DEI were compared with a prospective cohort of similar patients treated with EUS-FNI. Repeat endoscopy after index treatment was performed 3 months later or earlier if rebleeding occurred. The main outcomes assessed were rates of GV or overall rebleeding and adverse events. Results Forty patients (mean age 57.2 ± 9.1 years, 73% male) and 64 patients (mean age 58.0 ± 12.5 years, 52% male) underwent DEI and EUS-FNI, respectively. Compared to the DEI group, the frequency of isolated gastric varices type 1 (IGV1) were higher (p < 0.001) but MELD scores were lower (p = 0.004) in the EUS-FNI group. At index endoscopy, EUS-FNI utilized a lower mean volume of cyanoacrylate (2.0 ± 0.8 mL vs. 3.3 ± 1.3 mL; p < 0.001) and injected a greater number of varices (1.6 ± 0.7 vs. 1.1 ± 0.4; p < 0.001) compared to DEI. Overall, GV rebleeding [5/57 (8.8%) vs. 9/38 (23.7%); p = 0.045] and non-GV-related gastrointestinal bleeding [7/64 (10.9%) vs. 11/40 (27.5%); p = 0.030] were less frequent in the EUS-FNI group compared to the DEI group, respectively. Adverse event rates were similar (20.3% vs. 17.5%, p = 0.723). Conclusions EUS-guided CYA injection of active or recently bleeding GV in patients with portal hypertension appears to decrease the rate of GV rebleeding despite injection of more varices and less CYA volume during the initial endoscopic procedure. Adverse events are similar between the two groups. EUS-FNI appears to be the preferred strategy for treatment of these patients.
Hospital frailty risk score is superior to legacy comorbidity indices for risk adjustment of in-hospital cirrhosis cases
(Elsevier, 2023-11-03) Desai, Archita P.; Parvataneni, Swetha; Knapp, Shannon M.; Nephew, Lauren D.; Chalasani, Naga; Ghabril, Marwan S.; Orman, Eric S.; Medicine, School of Medicine
Background & aims: The hospital frailty risk score (HFRS) identifies older patients at risk of poor outcomes and may have value in cirrhosis. We compared the Charlson (CCI), Elixhauser (ECI), and cirrhosis (CirCom) comorbidity indices with the HFRS in predicting outcomes for cirrhosis hospitalisations. Methods: Using the National Inpatient Sample (quarter 4 of 2015-2019), we analysed cirrhosis hospitalisations. For each index, we described the prevalence of comorbid conditions and inpatient mortality. We compared the ability of CCI, ECI, CirCom, and HFRS to predict inpatient mortality. Raw and adjusted models predicting inpatient mortality were compared using the area under the receiver operating characteristic curve and the Akaike information criterion. Results: The cohort's (N = 626,553) median age was 61 years (IQR 52-68 years), 60% were male, cirrhosis was caused by alcohol in 43%, and 38% had ascites. The median comorbidity scores are as follows: ECI 4 (IQR 3-6), CCI 5 (IQR 4-8), and HFRS 5.6 (IQR 3.0-8.6). The most common CirCom score was 0 + 0 (44%). Across the range of values of each index, we observed different mortality ranges: CCI 1.9-13.1%, ECI 3.2-8.7%, CirCom 4.9-13.8%, and HFRS 1.0-15.2%. An adjusted model with HFRS had the highest area under the receiver operating characteristic curve in predicting mortality (HFRS 0.782 vs. ECI 0.689, CCI 0.695, and CirCom 0.692). We observed substantial variation in mortality with HFRS within each level of CCI, ECI, and CirCom. For example, for ECI 4, mortality increased from 0.6 to 16.4%, as HFRS increased from 0 to 15. Conclusions: Comorbidity indices predict inpatient cirrhosis mortality, but HFRS performs better than CCI, ECI, and CirCom. HFRS is an ideal tool for measuring comorbidity burden and disease severity risk adjustment in cirrhosis-related administrative database studies. Impact and implications: We compared commonly used comorbidity indices to a more recently described risk score (hospital frailty risk score [HFRS]) in patients with cirrhosis using a national sample of hospital records. Comorbid conditions are common in hospitalised patients with cirrhosis. There is significant variability in mortality across the range of each index. HFRS outperforms the Charlson comorbidity index, Elixhauser comorbidity index, and CirCom (cirrhosis-specific comorbidity scoring system) in predicting inpatient mortality. HFRS is a valuable index for risk adjustment in inpatient administrative database studies.
Hospital-Acquired Versus Community-Acquired Acute Kidney Injury in Patients with Cirrhosis: A Prospective Study
(Wolters Kluwer, 2020-09) Patidar, Kavish R.; Shamseddeen, Hani; Xu, Chenjia; Ghabril, Marwan S.; Nephew, Lauren D.; Desai, Archita P.; Anderson, Melissa; El-Achkar, Tarek M.; Ginès, Pere; Chalasani, Naga P.; Orman, Eric S.; Medicine, School of Medicine
Introduction: In patients with cirrhosis, differences between acute kidney injury (AKI) at the time of hospital admission (community-acquired) and AKI occurring during hospitalization (hospital-acquired) have not been explored. We aimed to compare patients with hospital-acquired AKI (H-AKI) and community-acquired AKI (C-AKI) in a large, prospective study. Methods: Hospitalized patients with cirrhosis were enrolled (N = 519) and were followed for 90 days after discharge for mortality. The primary outcome was mortality within 90 days; secondary outcomes were the development of de novo chronic kidney disease (CKD)/progression of CKD after 90 days. Cox proportional hazards and logistic regressions were used to determine the independent association of either AKI for primary and secondary outcomes, respectively. Results: H-AKI occurred in 10%, and C-AKI occurred in 25%. In multivariable Cox models adjusting for significant confounders, only patients with C-AKI had a higher risk for mortality adjusting for model for end-stage liver disease-Na: (hazard ratio 1.64, 95% confidence interval [CI] 1.04-2.57, P = 0.033) and adjusting for acute on chronic liver failure: (hazard ratio 2.44, 95% CI 1.63-3.65, P < 0.001). In univariable analysis, community-acquired-AKI, but not hospital-acquired-AKI, was associated with de novo CKD/progression of CKD (odds ratio 2.13, 95% CI 1.09-4.14, P = 0.027), but in multivariable analysis, C-AKI was not independently associated with de novo CKD/progression of CKD. However, when AKI was dichotomized by stage, C-AKI stage 3 was independently associated with de novo CKD/progression of CKD (odds ratio 4.79, 95% CI 1.11-20.57, P = 0.035). Discussion: Compared with H-AKI, C-AKI is associated with increased mortality and de novo CKD/progression of CKD in patients with cirrhosis. Patients with C-AKI may benefit from frequent monitoring after discharge to improve outcomes.
Impact of Recipient Age in Combined Liver-Kidney Transplantation: Caution Is Needed for Patients ≥70 Years
(Wolters Kluwer, 2020-06) Ekser, Burcin; Goggins, William C.; Fridell, Jonathan A.; Mihaylov, Plamen; Mangus, Richard S.; Lutz, Andrew J.; Soma, Daiki; Ghabril, Marwan S.; Lacerda, Marco A.; Powelson, John A.; Kubal, Chandrashekhar A.; Surgery, School of Medicine
Background. Elderly recipients (≥70 y) account for 2.6% of all liver transplants (LTs) in the United States and have similar outcomes as younger recipients. Although the rate of elderly recipients in combined liver-kidney transplant (CLKT) is similar, limited data are available on how elderly recipients perform after CLKT. Methods. We have previously shown excellent outcomes in CLKT using delayed kidney transplant (Indiana) Approach (mean kidney cold ischemia time = 53 ± 14 h). Between 2007 and 2018, 98 CLKTs were performed using the Indiana Approach at Indiana University (IU) and the data were retrospectively analyzed. Recipients were subgrouped based on their age: 18–45 (n = 16), 46–59 (n = 34), 60–69 (n = 40), and ≥70 years (n = 8). Results. Overall, more elderly patients received LT at IU (5.2%) when compared nationally (2.6%). The rate of elderly recipients in CLKT at IU was 8.2% (versus 2% Scientific Registry of Transplant Recipient). Recipient and donor characteristics were comparable between all age groups except recipient age and duration of dialysis. Patient survival at 1 and 3 years was similar among younger age groups, whereas patient survival was significantly lower in elderly recipients at 1 (60%) and 3 years (40%) (P = 0.0077). Control analyses (replicating Scientific Registry of Transplant Recipient’s survival stratification: 18–45, 46–64, ≥65 y) showed similar patient survival in all age groups. Conclusions. Although LT can be safely performed in elderly recipients, extreme caution is needed in CLKT due to the magnitude of operation.

Browsing by Author "Ghabril, Marwan S."

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