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Utility of scores to predict alcohol use after liver transplant: Take them with a grain of salt

Houston, Kevin; Duong, Nikki; Sterling, Richard K; Asgharpour, Amon; Bullock, Sheila; Weinland, Stephan; Keller, Nicole; Smirnova, Ekaterina; Khan, Hiba; Matherly, Scott; Wedd, Joel; Lee, Hannah; Siddiqui, Mohammad; Patel, Vaishali; Arias, Albert; Kumaran, Vinay; Lee, Seung; Sharma, Amit; Khan, Aamir; Imai, Daisuke; Levy, Marlon; Bruno, David
The Sustained Alcohol use post-Liver Transplant (SALT) and the High-Risk Alcohol Relapse (HRAR) scores were developed to predict a return to alcohol use after a liver transplant (LT) for alcohol-associated liver disease. A retrospective analysis of deceased donor LT from October 2018 to April 2022 was performed. All patients underwent careful pre-LT psychosocial evaluation. Data on alcohol use, substance abuse, prior rehabilitation, and legal issues were collected. After LT, all were encouraged to participate in rehabilitation programs and underwent interval phosphatidylethanol testing. Patients with alcohol-associated liver disease were stratified by < or > 6 months of sobriety before listing. Those with <6 months were further stratified as acute alcoholic hepatitis (AH) by NIAAA criteria and non-AH. The primary outcome was the utility of the SALT (<5 vs. ≥5) and HRAR (<3 vs. ≥3) scores to predict a return to alcohol use (+phosphatidylethanol) within 1 year after LT. Of the 365 LT, 86 had > 6 months of sobriety, and 85 had <6 months of sobriety; 41 with AH and 44 non-AH. In those with AH, the mean time of abstinence to LT was 58 days, and 71% failed prior rehabilitation. Following LT, the return to drinking was similar in the AH (24%) compared to <6-month non-AH (15%) and >6-month alcohol-associated liver disease (22%). Only 4% had returned to heavy drinking. The accuracy of both the SALT and HRAR scores to predict a return to alcohol was low (accuracy 61%-63%) with poor sensitivity (46% and 37%), specificity (67%-68%), positive predictive value (22%-26%) with moderate negative predictive value (81%-83%), respectively with higher negative predictive values (95%) in predicting a return to heavy drinking. Both SALT and HRAR scores had good negative predictive value in identifying patients at low risk for recidivism.
PMID: 38775570
ISSN: 1527-6473
CID: 5923302

Vibration-Controlled Transient Elastography-Based Parameters Predict Clinical Outcomes in Liver Transplant Recipients

Baral, Alok; Garg, Shreya; Nguyen, Madison; Razzaq, Rehan; Ang, Audrey; Khan, Hiba; Vainer, Dylan; Patel, Vaishali; Roache, Geneva; Muthiah, Mark; Yakubu, Idris; Kumaran, Vinay; Bui, Anh T; Siddiqui, Mohammad Shadab
BACKGROUND AND AIMS/OBJECTIVE:Vibration-controlled transient elastography (VCTE) is used in clinical practice to risk-stratify liver transplant (LT) recipients; however, there are currently little data demonstrating the relationship between VCTE and clinical outcomes. METHODS:A total of 362 adult LT recipients with successful VCTE examination between 2015 and 2022 were included. Presence of advanced fibrosis was defined as liver stiffness measurement (LSM) ≥10.5 kPa and hepatic steatosis as controlled attenuation parameter (CAP) ≥270 dB/m. The outcomes of interest included all-cause mortality, myocardial infarction (MI), and graft cirrhosis using cumulative incidence analysis that accounted for the competing risks of these outcomes. RESULTS:The LSM was elevated in 64 (18%) and CAP in 163 (45%) LT recipients. The baseline LSM values were similar in patients with elevated vs normal CAP values. After a median follow-up of 65 (interquartile range, 20-140) months from LT to baseline VCTE, 66 (18%) patients died, 12 (3%) developed graft cirrhosis, and 18 (5%) experienced an MI. Baseline high LSM was independently associated with all-cause mortality (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.11-3.50; P = .02) and new onset cirrhosis (HR, 6.74; 95% CI, 2.08-21.79; P < .01). A higher CAP value was significantly and independently associated with increased risk of experiencing a MI over study follow-up (HR, 4.14; 95% CI, 1.29-13.27; P = .017). CONCLUSIONS:The VCTE-based parameters are associated with clinical outcomes and offer the potential to be incorporated into clinical risk-stratification strategies to improve outcomes among LT recipients.
PMID: 38969073
ISSN: 1542-7714
CID: 5923312

Burden of Portal Hypertension Complications Is Greater in Liver Transplant Wait-Listed Registrants with End-Stage Liver Disease and Type 2 Diabetes

Yakubu, Idris; Flynn, Sean; Khan, Hiba; Nguyen, Madison; Razzaq, Rehan; Patel, Vaishali; Kumaran, Vinay; Sharma, Amit; Siddiqui, Mohammad Shadab
BACKGROUND AND AIMS/OBJECTIVE:Impact of type 2 diabetes mellitus (T2DM) in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT) remains poorly defined. The objective of the present study is to evaluate the relationship between T2DM and clinical outcomes among patients with LT waitlist registrants. We hypothesize that the presence of T2DM will be associated with worse clinical outcomes. METHODS:593 patients adult (age 18 years or older) who were registered for LT between 1/2010 and 1/2017 were included in this retrospective analysis. The impact of T2DM on liver-associated clinical events (LACE), survival, hospitalizations, need for renal replacement therapy, and likelihood of receiving LT were evaluated over a 12-month period. LACE was defined as variceal hemorrhage, hepatic encephalopathy, and ascites. Kaplan-Meier and Cox regression analysis were used to determine the association between T2DM and clinical outcomes. RESULTS:The baseline prevalence of T2DM was 32% (n = 191) and patients with T2DM were more likely to have esophageal varices (61% vs. 47%, p = 0.002) and history of variceal hemorrhage (23% vs. 16%, p = 0.03). The presence of T2DM was associated with increased risk of incident ascites (HR 1.91, 95% CI 1.11, 3.28, p = 0.019). Patients with T2DM were more likely to require hospitalizations (56% vs. 49%, p = 0.06), hospitalized with portal hypertension-related complications (22% vs. 14%; p = 0.026), and require renal replacement therapy during their hospitalization. Patients with T2DM were less likely to receive a LT (37% vs. 45%; p = 0.03). Regarding MELD labs, patients with T2DM had significantly lower bilirubin at each follow-up; however, no differences in INR and creatinine were noted. CONCLUSION/CONCLUSIONS:Patients with T2DM are at increased risk of clinical outcomes. This risk is not captured in MELD score, which may potentially negatively affect their likelihood of receiving LT.
PMCID:11415399
PMID: 38987444
ISSN: 1573-2568
CID: 5923322

Liver transplant recipients have worse metabolic body phenotype compared with matched non-transplant controls

Bhati, Chandra; Kirkman, Danielle; Forsgren, Mikael F; Kamal, Hiba; Khan, Hiba; Boyett, Sherry; Leinhard, Olof Dahlqvist; Linge, Jennifer; Patel, Vaishali; Patel, Samarth; Wolver, Susan; Siddiqui, Mohammad S
BACKGROUND AND AIM/UNASSIGNED:Quantification of body compartments, particularly the interaction between adipose tissue and skeletal muscle, is emerging as novel a biomarker of metabolic health. The present study evaluated the impact of liver transplant (LT) on body compartments. METHODS/UNASSIGNED:Totally 66 adult LT recipients were enrolled in whom body compartments including visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), muscle fat infiltration (MFI), fat-free muscle volume (FFMV), and liver fat (LF) were quantified via whole body magnetic resonance imaging (MRI). To provide non-LT comparison, each LT recipient was matched to at least 150 non-LT controls for same sex, age, and body mass index (BMI) from the UK Biobank registry. RESULTS/UNASSIGNED: = 0.189). Finally, compared with matched non-LT controls, patients transplanted for MASH cirrhosis had higher ASAT and VAT; however, FFMV and MFI were similar. CONCLUSION/UNASSIGNED:Using non-LT controls, the current study established the higher-than-expected adiposity burden among LT recipients, which is even higher among patients transplanted for MASH cirrhosis. These findings provide data needed to design future studies developing radiomics-based risk-stratification strategies in LT recipients.
PMCID:11420625
PMID: 39318868
ISSN: 2397-9070
CID: 5923332

Development of Clinical Algorithm Utilizing Vibration-Controlled Transient Elastography to Detect Advanced Hepatic Fibrosis in Liver Transplant Recipients

Arshad, Tamoore; Vainer, Dylan; Khan, Hiba; Baral, Alok; Garg, Shreya; Ang, Audrey; Patel, Vaishali; Kumaran, Vinay; Bruno, David; Lee, Seung; Sharma, Amit; Muthiah, Mark; Bui, Anh T; Siddiqui, Mohammad Shadab
INTRODUCTION/BACKGROUND:Vibration-controlled transient elastography (VCTE) based liver stiffness measurement (LSM) is an excellent 'rule-out' test for advanced hepatic fibrosis in liver transplant (LT) recipients, however, its ability to 'rule-in' the disease is suboptimal. The study aimed to improve diagnostic performance of LSM in LT recipients. METHODS:Adult LT recipients with a liver biopsy and VCTE were included (N = 150). Sequential covering analysis was performed to create rules to identify patients at low or high risk for advanced fibrosis (stage 3-4). RESULTS:Advanced hepatic fibrosis was excluded in patients with either LSM < 7.45 kPa (n = 72) or 7.45 ≤ LSM < 12.1 kPa and time from LT < 5.6 years (n = 25). Conversely, likelihood of advanced fibrosis was 95% if patients had LSM > 14.1 and controlled attenuation parameter > 279 dB/m (n = 21). Thus, 118 (79%) were correctly identified and 32 (21%) would have required a biopsy to establish the diagnosis. Compared to previously established LSM based cutoff values of 10.5 kPa (Youden index) and 13.3 kPa (maximized specificity), the false positive rates of sequential covering analysis was 1% compared to 16.5% with LSM ≥ 10.5 kPa and 8.3% with LSM ≥ 13.3 kPa. The true positive rates were comparable at 87% for sequential covering analysis, 93% for LSM ≥ 10.5 kPa and 83% for LSM ≥ 13.3 kPa. CONCLUSION/CONCLUSIONS:The proposed clinical sequential covering analysis allows for better risk stratification when evaluating for advanced fibrosis in LT recipients compared to LSM alone. Additional efforts are necessary to further reduce the number of patients with indeterminate results in whom a liver biopsy may be required.
PMCID:11098731
PMID: 38499735
ISSN: 1573-2568
CID: 5923292

Hepatic inflammation: an important target for biomarker development in nonalcoholic fatty liver disease [Comment]

Khan, Hiba; Siddiqui, Mohammad Shadab
PMID: 37351134
ISSN: 2304-3881
CID: 5923282

The impact of the COVID-19 pandemic on UK medical education. A nationwide student survey [Letter]

Tekkis, Nicholas Pari; Rafi, Damir; Brown, Sam; Courtney, Alona; Kawka, Michal; Howell, Ann-Marie; McLean, Kenneth; Gardiner, Matthew; Mavroveli, Stella; Hutchinson, Peter; Tekkis, Paris; Wilkinson, Paul; Sam, Amir H; Savva, Nicos; Kontovounisios, Christos; ,; ,; Tekkis, N; Rafi, D; Brown, S; Courtney, A; Kawka, M; Howell, A; McLean, K; Gardiner, M; Mavroveli, S; Hutchinson, P; Tekkis, P; Wilkinson, P; Sam, A H; Savva, N; Kontovounisios, C; ,; Tekkis, N; Rafi, D; Brown, S; Courtney, A; Kawka, M; Howell, A; McLean, K; Gardiner, M; Mavroveli, S; Hutchinson, P; Tekkis, P; Wilkinson, P; Sam, A H; Savva, N; Kontovounisios, C; ,; Tekkis, N; Brown, S; Kawka, M; Mclean, K; Savva, N; ,; Wilkinson, P; Sam, A H; ,; Singal, A; Chia, C; Chia, W; Ganesananthan, S; Ooi, S Z Y; Pengelly, S; Wellington, J; Mak, S; Subbiah Ponniah, H; Heyes, A; Aberman, I; Ahmed, T; Al-Shamaa, S; Appleton, L; Arshad, A; Awan, H; Baig, Q; Benedict, K; Berkes, S; Citeroni, N L; Damani, A; de Sancha, A; Fisayo, T; Gupta, S; Haq, M; Heer, B; Jones, A; Khan, H; Kim, H; Meiyalagan, N; Miller, G; Minta, N; Mirza, L; Mohamed, F; Ramjan, F; Read, P; Soni, L; Tailor, V; Tas, R N; Vorona, M; Walker, M; Winkler, T; Bardon, A; Acquaah, J; Ball, T; Bani, W; Elmasry, A; Hussein, F; Kolluri, M; Lusta, H; Newman, J; Nott, M; Perwaiz, M I; Rayner, R; Shah, A; Shaw, I; Yu, K; Cairns, M; Clough, R; Gaier, S; Hirani, D; Jeyapalan, T; Li, Y; Patel, C R; Shabir, H; Wang, Y A; Weatherhead, A; Dhiran, A; Renney, O; Wells, P; Ferguson, S; Joyce, A; Mergo, A; Adebayo, O; Ahmad, J; Akande, O; Ang, G; Aniereobi, E; Awasthi, S; Banjoko, A; Bates, J; Chibada, C; Clarke, N; Craner, I; Desai, D D; Dixon, K; Duffaydar, H I; Kuti, M; Mughal, A Z; Nair, D; Pham, M C; Preest, G G; Reid, R; Sachdeva, G S; Selvaratnam, K; Sheikh, J; Soran, V; Stoney, N; Wheatle, M; Howarth, K; Knapp-Wilson, A; Lee, K S; Mampitiya, N; Masson, C; McAlinden, J J; McGowan, N; Parmar, S C; Robinson, B; Wahid, S; Willis, L; Risquet, R; Adebayo, A; Dhingra, L; Kathiravelupillai, S; Narayanan, R; Soni, J; Ghafourian, P; Hounat, A; Lennon, K A; Abdi Mohamud, M; Chou, W; Chong, L; Graham, C J; Piya, S; Riad, A M; Vennard, S; Wang, J; Kawar, L; Maseland, C; Myatt, R; Tengku Saifudin, T N S; Yong, S Q; Douglas, F; Ogbechie, C; Sharma, K; Zafar, L; Bajomo, M O; Byrne, M H V; Obi, C; Oluyomi, D I; Patsalides, M A; Rajananthanan, A; Richardson, G; Clarke, A; Roxas, A; Adeboye, W; Argus, L; McSweeney, J; Rahman-Chowdhury, M; Hettiarachchi, D S; Masood, M T; Antypas, A; Thomas, M; de Andres Crespo, M; Zimmerman, M; Dhillon, A; Abraha, S; Burton, O; Jalal, A H B; Bailey, B; Casey, A; Kathiravelupillai, A; Missir, E; Boult, H; Campen, D; Collins, J M; Dulai, S; Elhassan, M; Foster, Z; Horton, E; Jones, E; Mahapatra, S; Nancarrow, T; Nyamapfene, T; Rimmer, A; Robberstad, M; Robson-Brown, S; Saeed, A; Sarwar, Y; Taylor, C; Vetere, G; Whelan, M K; Williams, J; Zahid, D; Chand, C; Matthews, M
PMID: 34428109
ISSN: 1466-187x
CID: 5940762

Dump the "dimorphism": Comprehensive synthesis of human brain studies reveals few male-female differences beyond size

Eliot, Lise; Ahmed, Adnan; Khan, Hiba; Patel, Julie
With the explosion of neuroimaging, differences between male and female brains have been exhaustively analyzed. Here we synthesize three decades of human MRI and postmortem data, emphasizing meta-analyses and other large studies, which collectively reveal few reliable sex/gender differences and a history of unreplicated claims. Males' brains are larger than females' from birth, stabilizing around 11 % in adults. This size difference accounts for other reproducible findings: higher white/gray matter ratio, intra- versus interhemispheric connectivity, and regional cortical and subcortical volumes in males. But when structural and lateralization differences are present independent of size, sex/gender explains only about 1% of total variance. Connectome differences and multivariate sex/gender prediction are largely based on brain size, and perform poorly across diverse populations. Task-based fMRI has especially failed to find reproducible activation differences between men and women in verbal, spatial or emotion processing due to high rates of false discovery. Overall, male/female brain differences appear trivial and population-specific. The human brain is not "sexually dimorphic."
PMID: 33621637
ISSN: 1873-7528
CID: 5923272