Browsing by Author "Gawrieh, Samer"
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Item A multisociety Delphi consensus statement on new fatty liver disease nomenclature(Wolters Kluwer, 2023) Rinella, Mary E.; Lazarus, Jeffrey V.; Ratziu, Vlad; Francque, Sven M.; Sanyal, Arun J.; Kanwal, Fasiha; Romero, Diana; Abdelmalek, Manal F.; Anstee, Quentin M.; Arab, Juan Pablo; Arrese, Marco; Bataller, Ramon; Beuers, Ulrich; Boursier, Jerome; Bugianesi, Elisabetta; Byrne, Christopher D.; Castro Narro, Graciela E.; Chowdhury, Abhijit; Cortez-Pinto, Helena; Cryer, Donna R.; Cusi, Kenneth; El-Kassas, Mohamed; Klein, Samuel; Eskridge, Wayne; Fan, Jiangao; Gawrieh, Samer; Guy, Cynthia D.; Harrison, Stephen A.; Kim, Seung Up; Koot, Bart G.; Korenjak, Marko; Kowdley, Kris V.; Lacaille, Florence; Loomba, Rohit; Mitchell-Thain, Robert; Morgan, Timothy R.; Powell, Elisabeth E.; Roden, Michael; Romero-Gómez, Manuel; Silva, Marcelo; Singh, Shivaram Prasad; Sookoian, Silvia C.; Spearman, C. Wendy; Tiniakos, Dina; Valenti, Luca; Vos, Miriam B.; Wong, Vincent Wai-Sun; Xanthakos, Stavra; Yilmaz, Yusuf; Younossi, Zobair; Hobbs, Ansley; Villota-Rivas, Marcela; Newsome, Philip N.; NAFLD Nomenclature consensus group; Medicine, School of MedicineThe principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.Item A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry(Wolters Kluwer, 2024-05-10) Schwantes-An, Tae-Hwi; Whitfield, John B.; Aithal, Guruprasad P.; Atkinson, Stephen R.; Bataller, Ramon; Botwin, Greg; Chalasani, Naga P.; Cordell, Heather J.; Daly, Ann K.; Darlay, Rebecca; Day, Christopher P.; Eyer, Florian; Foroud, Tatiana; Gawrieh, Samer; Gleeson, Dermot; Goldman, David; Haber, Paul S.; Jacquet, Jean-Marc; Lammert, Craig S.; Liang, Tiebing; Liangpunsakul, Suthat; Masson, Steven; Mathurin, Philippe; Moirand, Romain; McQuillin, Andrew; Moreno, Christophe; Morgan, Marsha Y.; Mueller, Sebastian; Müllhaupt, Beat; Nagy, Laura E.; Nahon, Pierre; Nalpas, Bertrand; Naveau, Sylvie; Perney, Pascal; Pirmohamed, Munir; Seitz, Helmut K.; Soyka, Michael; Stickel, Felix; Thompson, Andrew; Thursz, Mark R.; Trépo, Eric; Morgan, Timothy R.; Seth, Devanshi; GenomALC Consortium; Medical and Molecular Genetics, School of MedicineBackground: Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis. Methods: Using a data-driven approach, a PRS for ALC was generated using a meta-genome-wide association study of ALC (N=4305) and an independent cohort of heavy drinkers with ALC and without significant liver disease (N=3037). It was validated in 2 additional independent cohorts from the UK Biobank with diagnosed ALC (N=467) and high-risk drinking controls (N=8981) and participants in the Indiana Biobank Liver cohort with alcohol-associated liver disease (N=121) and controls without liver disease (N=3239). Results: A 20-single-nucleotide polymorphisms PRS for ALC (PRSALC) was generated that stratified risk for ALC comparing the top and bottom deciles of PRS in the 2 validation cohorts (ORs: 2.83 [95% CI: 1.82 -4.39] in UK Biobank; 4.40 [1.56 -12.44] in Indiana Biobank Liver cohort). Furthermore, PRSALC improved the prediction of ALC risk when added to the models of clinically known predictors of ALC risk. It also stratified the risk for metabolic dysfunction -associated steatotic liver disease -cirrhosis (3.94 [2.23 -6.95]) in the Indiana Biobank Liver cohort -based exploratory analysis. Conclusions: PRSALC incorporates 20 single-nucleotide polymorphisms, predicts increased risk for ALC, and improves risk stratification for ALC compared with the models that only include clinical risk factors. This new score has the potential for early detection of heavy drinking patients who are at high risk for ALC.Item ADH1B*2 is Associated With Reduced Severity of Nonalcoholic Fatty Liver Disease in Adults, Independent of Alcohol Consumption(Elsevier, 2020) Vilar-Gomez, Eduardo; Sookoian, Silvia; Pirola, Carlos Jose; Liang, Tiebing; Gawrieh, Samer; Cummings, Oscar; Liu, Wanqing; Chalasani, Naga; Medicine, School of MedicineBackground & Aims Alcohol dehydrogenase 1B (ADH1B) is involved in alcohol metabolism. The allele A ( ADH1B*2) of rs1229984: A>G variant in ADH1B is associated a higher alcohol metabolizing activity, compared to the ancestral allele G ( ADH1B*1). Moderate alcohol consumption is associated with reduced severity of nonalcoholic fatty liver disease (NAFLD), based on histologic analysis, compared with no alcohol consumption. However, it is unclear whether ADH1B*2 modifies the relationship between moderate alcohol consumption and severity of NAFLD. We examined the association between ADH1B*2 and moderate alcohol consumption and histologic severity of NAFLD. Methods We collected data from 1557 multi-ethnic adult patients with biopsy-proven NAFLD enrolled into 4 different studies conducted by the NASH Clinical Research Network. Histories of alcohol consumption were obtained from answers to standardized questionnaires. Liver biopsies were analyzed by histology and scored centrally according to the NASH CRN criteria. We performed covariate adjusted logistic regressions to identify associations between histologic features of NAFLD severity and moderate alcohol consumption and/or ADH1B*2. Results A higher proportion of Asians/Pacific Islanders/Hawaiians carried the ADH1B*2 allele (86%) than other racial groups (4%–13%). However, the study population comprised mostly non-Hispanic whites (1153 patients, 74%), so the primary analysis focused on this group. Among them, 433 were moderate drinkers and 90 were ADH1B*2 carriers. After we adjusted for confounders, including alcohol consumption status, ADH1B*2 was associated with lower frequency of steatohepatitis (odds ratio [OR], 0.52; P<.01) or fibrosis (odds ratio, 0.69; P=.050) compared with ADH1B*1. Moderate alcohol consumption (g/day) reduced the severity of NAFLD in patients with ADH1B*1 or ADH1B*2. However, ADH1B*2, compared to ADH1B*1, was associated with a reduced risk of definite NASH ( ADH1B*2 OR, 0.80; P<.01 vs ADH1B*1 OR, 0.96; P=.036) and a reduced risk of an NAFLD activity score of 4 or higher ( ADH1B*2 OR, 0.83; P=.012 vs ADH1B*1 OR, 0.96; P=.048) ( P<.01 for the difference in the effect of moderate alcohol consumption between alleles). The relationship between body mass index and NAFLD severity was significantly modified by ADH1B*2, even after we controlled for alcohol consumption. Conclusions ADH1B*2 reduces the risk of NASH and fibrosis in adults with NAFLD regardless of alcohol consumption status. ADH1B*2 might modify the association between high body mass index and NAFLD severity.Item Apolipoprotein B and PNPLA3 Double Heterozygosity in a Father–Son Pair With Advanced Nonalcoholic Fatty Liver Disease(Wiley, 2019) Jansson-Knodell, Claire L.; Gawrieh, Samer; McIntyre, Adam D.; Liang, Tiebing; Hegele, Robert A.; Chalasani, Naga; Medicine, School of MedicineItem Autoimmune Hepatitis in the Elderly: Diagnosis and Pharmacologic Management(Springer, 2018-07) Rizvi, Syed; Gawrieh, Samer; Medicine, School of MedicineAutoimmune hepatitis (AIH) may present as acute or chronic hepatitis in the elderly. Advanced hepatic fibrosis and cirrhosis are common on first presentation in this population. In this review, we discuss the presentation, approach to diagnosis and management of AIH in the elderly. As polypharmacy is common in the elderly, careful medication use history is essential for detecting drug-induced AIH-like hepatitis. Steroid-sparing or minimizing therapeutic regimens are preferred to treat AIH in the elderly. For the purpose of induction, budesonide or lower dose prednisone in combination with azathioprine (AZA) regimens are preferred over high-dose prednisone monotherapy due to the higher risk of side effects of the later in the elderly. The goal of maintenance therapy should be to achieve full biochemical and histologic remission. Bone density monitoring and interventions to prevent steroid-related bone disease should be implemented throughout the course of the disease. Liver transplantation should be considered in the elderly patient with liver failure or early hepatocellular carcinoma if there are no significant comorbidities or compromise in functional status.Item Automated assessment of steatosis in murine fatty liver(PLOS, 2018-05-10) Sethunath, Deepak; Morusu, Siripriya; Tuceryan, Mihran; Cummings, Oscar W.; Zhang, Hao; Yin, Xiao-Ming; Vanderbeck, Scott; Chalasani, Naga; Gawrieh, Samer; Computer and Information Science, School of ScienceAlthough mice are commonly used to study different aspects of fatty liver disease, currently there are no validated fully automated methods to assess steatosis in mice. Accurate detection of macro- and microsteatosis in murine models of fatty liver disease is important in studying disease pathogenesis and detecting potential hepatotoxic signature during drug development. Further, precise quantification of macrosteatosis is essential for quantifying effects of therapies. Here, we develop and validate the performance of automated classifiers built using image processing and machine learning methods for detection of macro- and microsteatosis in murine fatty liver disease and study the correlation of automated quantification of macrosteatosis with expert pathologist’s semi-quantitative grades. The analysis is performed on digital images of 27 Hematoxylin & Eosin stained murine liver biopsy samples. An expert liver pathologist scored the amount of macrosteatosis and also annotated macro- and microsteatosis lesions on the biopsy images using a web-application. Using these annotations, supervised machine learning and image processing techniques, we created classifiers to detect macro- and microsteatosis. For macrosteatosis prediction, the model’s precision, sensitivity and area under the receiver operator characteristic (AUROC) were 94.2%, 95%, 99.1% respectively. When correlated with pathologist’s semi-quantitative grade of steatosis, the model fits with a coefficient of determination value of 0.905. For microsteatosis prediction, the model has precision, sensitivity and AUROC of 79.2%, 77%, 78.1% respectively. Validation by the expert pathologist of classifier’s predictions made on unseen images of biopsy samples showed 100% and 63% accuracy for macro- and microsteatosis, respectively. This novel work demonstrates that fully automated assessment of steatosis is feasible in murine liver biopsies images. Our classifier has excellent sensitivity and accuracy for detection of macrosteatosis in murine fatty liver disease.Item Automatic classification of white regions in liver biopsies by supervised machine learning(Elsevier, 2014-04) Vanderbeck, Scott; Bockhorst, Joseph; Komorowski, Richard; Kleiner, David E.; Gawrieh, Samer; Medicine, School of MedicineAutomated assessment of histological features of non-alcoholic fatty liver disease (NAFLD) may reduce human variability and provide continuous rather than semiquantitative measurement of these features. As part of a larger effort, we perform automatic classification of steatosis, the cardinal feature of NAFLD, and other regions that manifest as white in images of hematoxylin and eosin-stained liver biopsy sections. These regions include macrosteatosis, central veins, portal veins, portal arteries, sinusoids and bile ducts. Digital images of hematoxylin and eosin-stained slides of 47 liver biopsies from patients with normal liver histology (n = 20) and NAFLD (n = 27) were obtained at 20× magnification. The images were analyzed using supervised machine learning classifiers created from annotations provided by two expert pathologists. The classification algorithm performs with 89% overall accuracy. It identified macrosteatosis, bile ducts, portal veins and sinusoids with high precision and recall (≥ 82%). Identification of central veins and portal arteries was less robust but still good. The accuracy of the classifier in identifying macrosteatosis is the best reported. The accurate automated identification of macrosteatosis achieved with this algorithm has useful clinical and research-related applications. The accurate detection of liver microscopic anatomical landmarks may facilitate important subsequent tasks, such as localization of other histological lesions according to liver microscopic anatomy.Item Automatic quantification of lobular inflammation and hepatocyte ballooning in nonalcoholic fatty liver disease liver biopsies(Elsevier, 2015) Vanderbeck, Scott; Bockhorst, Joseph; Kleiner, David; Komorowski, Richard; Chalasani, Naga; Gawrieh, Samer; Department of Medicine, IU School of MedicineAutomatic quantification of cardinal histologic features of nonalcoholic fatty liver disease (NAFLD) may reduce human variability and allow continuous rather than semiquantitative assessment of injury. We recently developed an automated classifier that can detect and quantify macrosteatosis with greater than or equal to 95% precision and recall (sensitivity). Here, we report our early results on the classifier's performance in detecting lobular inflammation and hepatocellular ballooning. Automatic quantification of lobular inflammation and ballooning was performed on digital images of hematoxylin and eosin–stained slides of liver biopsy samples from 59 individuals with normal liver histology and varying severity of NAFLD. Two expert hepatopathologists scored liver biopsies according the nonalcoholic steatohepatitis clinical research network scoring system and provided annotations of lobular inflammation and hepatocyte ballooning on the digital images. The classifier had precision and recall of 70% and 49% for lobular inflammation, and 91% and 54% for hepatocyte ballooning. In addition, the classifier had an area under the curve of 95% for lobular inflammation and 98% for hepatocyte ballooning. The Spearman rank correlation coefficient for comparison with pathologist grades was 45.2% for lobular inflammation and 46% for hepatocyte ballooning. Our novel observations demonstrate that automatic quantification of cardinal NAFLD histologic lesions is feasible and offer promise for further development of automatic quantification as a potential aid to pathologists evaluating NAFLD biopsies in clinical practice and clinical trials.Item Changing Trends of Cirrhotic and Noncirrhotic Hepatocellular Carcinoma in the Era of Directly-Acting Antiviral Agents(Wolters Kluwer, 2021-11-03) Mathur, Karan; Mazhar, Areej; Patel, Milin; Dakhoul, Lara; Burney, Heather; Liu, Hao; Nephew, Lauren; Chalasani, Naga; deLemos, Andrew; Gawrieh, Samer; Medicine, School of MedicineIntroduction: The impact of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) on burden of cirrhotic and noncirrhotic hepatocellular carcinoma (HCC) has not been examined. We assessed recent trends in liver disease etiologies of HCC and proportion of noncirrhotic HCC since DAAs introduction. Methods: Clinical characteristics including presence or absence of underlying cirrhosis were collected from 2,623 patients diagnosed with HCC between 2009 and 2019 at 2 large US centers. Logistic regression was performed to investigate the annual trends of HCC due to different liver diseases and proportions of noncirrhotic cases. Results: In the DAA era (2014-2019), annual decline in HCV-HCC (odds ratio [OR] = 0.93, 95% confidence interval [CI] 0.88-0.99, P = 0.019), without change in trends of other liver diseases-related HCC, was observed. Annual increase in noncirrhotic HCC (OR 1.13, 95% CI 1.03-1.23, P = 0.009) and decline in cirrhotic HCC (OR 0.89, 95% CI 0.81-0.97, P = 0.009) along with similar trends for HCV-HCC-increase in noncirrhotic cases (OR 1.35, 95% CI 1.08-1.69, P = 0.009) and decrease in cirrhotic cases (OR 0.92, 95% CI 0.86-0.98, P = 0.012)-were observed during the DAA era. Compared with the pre-DAA era, HCC resection rate increased (10.7% vs 14.0%, P = 0.013) whereas liver transplantation rate decreased (15.1% vs 12.0%, P = 0.023) in the DAA era. Discussion: Since introduction of DAAs, proportions of cirrhotic HCC have decreased, whereas proportions of noncirrhotic HCC have increased. These new trends were associated with change in utilization of liver resection and transplantation for HCC. The impact of changing patterns of DAA use on these trends will require further study.Item Characteristics, aetiologies and trends of hepatocellular carcinoma in patients without cirrhosis: A United States multicentre study(Wiley, 2019-10) Gawrieh, Samer; Dakhoul, Lara; Miller, Ethan; Scanga, Andrew; deLemos, Andrew; Kettler, Carla; Burney, Heather; Liu, Hao; Abu-Sbeih, Hamzah; Chalasani, Naga; Wattacheril, Julia; Medicine, School of MedicineBackground Limited data exist on the burden and features of non‐cirrhotic hepatocellular carcinoma (HCC) in the United States. Aim To evaluate characteristics, aetiologies, trends and outcomes of non‐cirrhotic HCC from 2000 to 2014 at five large US centres Methods Patient, tumour and liver disease aetiology data were collected. The presence of underlying cirrhosis was assessed based on published criteria. Results Of 5144 eligible patients with HCC, 11.7% had no underlying cirrhosis. Non‐cirrhotic patients were older (64.1 vs 61.2 years), more frequently females (33.9% vs 20.8%) and less frequently black (8.3% vs 12.4%) (P < .001 for all). Among non‐cirrhotic patients, non‐alcoholic fatty liver disease (NAFLD) was the most common liver disease (26.3%), followed by hepatitis C virus (HCV) (12.1%) and hepatitis B virus (HBV) (10%) infections. As of 2014, there was increased percentage of cirrhotic HCC and a decline in non‐cirrhotic HCC mainly due to significant annual increases in cirrhotic HCC due to HCV (0.96% [P < .0001]) and NAFLD (0.66% [P = .003]). Patients with non‐cirrhotic HCC had larger tumours (8.9 vs 5.3 cm), were less frequently within Milan criteria (15% vs 39%), more frequently underwent resection (43.6% vs 8%) (P < .001 for all) and had better overall survival than cirrhotic HCC patients (median 1.8 vs 1.3 years, P = .004). Conclusions Nearly 12% of HCCs occurred in patients without underlying cirrhosis. NAFLD was the most common liver disease in these patients. During the study, the frequency of non‐cirrhotic HCC decreased, whereas that of cirrhotic HCC increased. Although non‐cirrhotic patients presented with more advanced HCC, their survival was better.