Browsing by Subject "Liver disease"
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Item Causality Assessment for Suspected Drug-Induced Liver Injury in Patients With Underlying Chronic Liver Disease(Wiley, 2017-03-30) Dakhoul, Lara; Chalasani, Naga; Medicine, School of MedicineItem Clarifying the HOPE Act landscape: The challenge of donors with false-positive HIV results(Wiley, 2020-02) Durand, Christine M.; Werbel, William; Doby, Brianna; Brown, Diane; Desai, Niraj M.; Malinis, Maricar; Price, Jennifer; Chin-Hong, Peter; Mehta, Shikha; Friedman-Moraco, Rachel; Turgeon, Nicole A.; Gilbert, Alexander; Morris, Michele I.; Stosor, Valentina; Elias, Nahel; Aslam, Saima; Santos, Carlos A.Q.; Hand, Jonathan M.; Husson, Jennifer; Pruett, Timothy L.; Agarwal, Avinash; Adebiyi, Oluwafisayo; Pereira, Marcus; Small, Catherine B.; Apewokin, Senu; Lee, Dong Heun; Haidar, Ghady; Blumberg, Emily; Mehta, Sapna A.; Huprikar, Shirish; Florman, Sander S.; Redd, Andrew D.; Tobian, Aaron A.R.; Segev, Dorry L.; Medicine, School of MedicineItem Clinical conundrum: managing iron overload after renal transplantation(BMJ, 2021-02-05) Upadhyay, Binayak; Green, Steven D.; Khanal, Nabin; Antony, Aśok C.; Medicine, School of MedicineIatrogenic iron overload, which is not uncommon in patients undergoing long-term haemodialysis, arises from a combination of multiple red cell transfusions and parenteral iron infusions that are administered to maintain a haemoglobin concentration of approximately 10 g/dL. Although iron overload due to genetic haemochromatosis is conventionally managed by phlebotomy, patients with haemoglobinopathies and chronic transfusion-induced iron overload are treated with iron-chelation therapy. However, the management of iron overload in our patient who presented with hepatic dysfunction and immunosuppressive drug-induced mild anaemia in the post-renal transplant setting posed unique challenges. We report on the decision-making process used in such a case that led to a successful clinical resolution of hepatic iron overload through the combined use of phlebotomy and erythropoiesis stimulating agents, while avoiding use of iron-chelating agents that could potentially compromise both hepatic and renal function.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 The FATZO mouse, a next generation model of type 2 diabetes, develops NAFLD and NASH when fed a Western diet supplemented with fructose(BMC, 2019-03-18) Sun, Gao; Jackson, Charles V.; Zimmerman, Karen; Zhang, Li-Kun; Finnearty, Courtney M.; Sandusky, George E.; Zhang, Guodong; Peterson, Richard G.; Wang, Yi-Xin (Jim); Pathology and Laboratory Medicine, School of MedicineMetabolic disorders such as insulin resistance, obesity, and hyperglycemia are prominent risk factors for the development of non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH). Dietary rodent models employ high fat, high cholesterol, high fructose, methionine/choline deficient diets or combinations of these to induce NAFLD/NASH. The FATZO mice spontaneously develop the above metabolic disorders and type 2 diabetes (T2D) when fed with a normal chow diet. The aim of the present study was to determine if FATZO mice fed a high fat and fructose diet would exacerbate the progression of NAFLD/NASH. METHODS: Male FATZO mice at the age of 8 weeks were fed with high fat Western diet (D12079B) supplemented with 5% fructose in the drinking water (WDF) for the duration of 20 weeks. The body weight, whole body fat content, serum lipid profiles and liver function markers were examined monthly along with the assessment of liver histology for the development of NASH. In addition, the effects of obeticholic acid (OCA, 30 mg/kg, QD) on improvement of NASH progression in the model were evaluated. RESULTS: Compared to normal control diet (CD), FATZO mice fed with WDF were heavier with higher body fat measured by qNMR, hypercholesterolemia and had progressive elevations in AST (~ 6 fold), ALT (~ 6 fold), liver over body weight (~ 2 fold) and liver triglyceride (TG) content (1.4-2.9 fold). Histological examination displayed evidence of NAFLD/NASH, including hepatic steatosis, lobular inflammation, ballooning and fibrosis in FATZO mice fed WDF. Treatment with OCA for 15 weeks in FATZO mice on WDF significantly alleviated hypercholesterolemia and elevation of AST/ALT, reduced liver weight and liver TG contents, attenuated hepatic ballooning, but did not affect body weight and blood TG levels. CONCLUSION: WDF fed FATZO mice represent a new model for the study of progressive NAFLD/NASH with concurrent metabolic dysregulation.Item From detection to intervention, optimizing care for patients with alcohol use disorder and advanced hepatic fibrosis(Wiley, 2024) Zuluaga, Paola; Liangpunsakul, Suthat; Medicine, School of MedicineItem Hepatitis C: From inflammatory pathogenesis to anti-inflammatory/hepatoprotective therapy(Baishideng Publishing Group, 2018-12-21) Li, Hu; Huang, Meng-Hao; Jiang, Jian-Dong; Peng, Zong-Gen; Medicine, School of MedicineHepatitis C virus (HCV) infection commonly causes progressive liver diseases that deteriorate from chronic inflammation to fibrosis, cirrhosis and even to hepatocellular carcinoma. A long-term, persistent and uncontrolled inflammatory response is a hallmark of these diseases and further leads to hepatic injury and more severe disease progression. The levels of inflammatory cytokines and chemokines change with the states of infection and treatment, and therefore, they may serve as candidate biomarkers for disease progression and therapeutic effects. The mechanisms of HCV-induced inflammation involve classic pathogen pattern recognition, inflammasome activation, intrahepatic inflammatory cascade response, and oxidative and endoplasmic reticulum stress. Direct-acting antivirals (DAAs) are the first-choice therapy for effectively eliminating HCV, but DAAs alone are not sufficient to block the uncontrolled inflammation and severe liver injury in HCV-infected individuals. Some patients who achieve a sustained virologic response after DAA therapy are still at a long-term risk for progression to liver cirrhosis and hepatocellular carcinoma. Therefore, coupling with anti-inflammatory/hepatoprotective agents with anti-HCV effects is a promising therapeutic regimen for these patients during or after treatment with DAAs. In this review, we discuss the relationship between inflammatory mediators and HCV infection, summarize the mechanisms of HCV-induced inflammation, and describe the potential roles of anti-inflammatory/hepatoprotective drugs with anti-HCV activity in the treatment of advanced HCV infection.Item Mast cells in liver disease progression: An update on current studies and implications(Wiley, 2021-08) Pham, Linh; Kennedy, Lindsey; Baiocchi, Leonardo; Meadows, Vik; Ekser, Burcin; Kundu, Debjyoti; Zhou, Tianhao; Sato, Keisaku; Glaser, Shannon; Ceci, Ludovica; Alpini, Gianfranco; Francis, Heather; Medicine, School of MedicineItem Murine study of portal hypertension associated endothelin-1 hypo-response(Baishideng Publishing Group, 2015-04-28) Theodorakis, Nicholas; Maluccio, Mary; Skill, Nicholas; Department of Medicine, IU School of MedicineAIM: To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes. METHODS: Wild type, eNOS(-/-) and iNOS(-/-) mice received partial portal vein ligation surgery to induce portal hypertension or sham surgery. Development of portal hypertension was determined by measuring the splenic pulp pressure, abdominal aortic flow and portal systemic shunting. To measure splenic pulp pressure, a microtip pressure transducer was inserted into the spleen pulp. Abdominal aortic flow was measured by placing an ultrasonic Doppler flow probe around the abdominal aorta between the diaphragm and celiac artery. Portal systemic shunting was calculated by injection of fluorescent microspheres in to the splenic vein and determining the percentage accumulation of spheres in liver and pulmonary beds. Endothelin-1 hypo-response was evaluated by measuring the change in abdominal aortic flow in response to endothelin-1 intravenous administration. In addition, thoracic aorta endothelin-1 contraction was measured in 5 mm isolated thoracic aorta rings ex-vivo using an ADI small vessel myograph. RESULTS: In wild type and iNOS(-/-) mice splenic pulp pressure increased from 7.5 ± 1.1 mmHg and 7.2 ± 1 mmHg to 25.4 ± 3.1 mmHg and 22 ± 4 mmHg respectively. In eNOS(-/-) mice splenic pulp pressure was increased after 1 d (P = NS), after which it decreased and by 7 d was not significantly elevated when compared to 7 d sham operated controls (6.9 ± 0.6 mmHg and 7.3 ± 0.8 mmHg respectively, P = 0.3). Abdominal aortic flow was increased by 80% and 73% in 7 d portal vein ligated wild type and iNOS when compared to shams, whereas there was no significant difference in 7 d portal vein ligated eNOS(-/-) mice when compared to shams. Endothelin-1 induced a rapid reduction in abdominal aortic blood flow in wild type, eNOS(-/-) and iNOS(-/-) sham mice (50% ± 8%, 73% ± 9% and 47% ± 9% respectively). Following portal vein ligation endothelin-1 reduction in blood flow was significantly diminished in each mouse group. Abdominal aortic flow was reduced by 19% ± 9%, 32% ± 10% and 9% ± 9% in wild type, eNOS(-/-) and iNOS(-/-) mice respectively. CONCLUSION: Aberrant endothelin-1 response in murine portal hypertension is NOS isoform independent. Moreover, portal hypertension in the portal vein ligation model is independent of ET-1 function.Item Performance of race-neutral eGFR equations in patients with decompensated cirrhosis(Wolters Kluwer, 2025) Fallahzadeh, Mohammad Amin; Allegretti, Andrew S.; Nadim, Mitra K.; Mahmud, Nadim; Patidar, Kavish R.; Cullaro, Giuseppe; Saracino, Giovanna; Asrani, Sumeet K.; Medicine, School of MedicineThe 2021 Chronic Kidney Disease Epidemiology Collaboration equation [CKD-EPI 2021] is a race-neutral equation recently developed and rapidly implemented as a reference standard to estimate glomerular filtration rate(GFR). However, its role in cirrhosis has not been examined especially in low GFR. We analyzed the performance of CKD-EPI 2021 compared to other equations with protocol-measured GFR (mGFR) in cirrhosis. We analyzed 2090 unique adult patients with cirrhosis undergoing protocol GFR measurements using iothalamate clearance from 1985 to 2015 when listed for liver transplantation at Baylor University in Dallas and Fort Worth, Texas. Using mGFR as a reference standard, the CKD-EPI 2021 was compared to CKD-EPI 2012, Modification of Diet in Renal Disease-4, Modification of Diet in Renal Disease-6, Royal Free Hospital, and GFR Assessment in Liver disease overall and in certain subgroups (ascites, mGFR ≤ 30 mL/min/1.73 m 2 , diagnosis, Model for End-Stage Liver Disease and gender). We examined bias (difference between eGFR and mGFR), accuracy (p30: eGFR within ± 30% of mGFR) and agreement between eGFR and mGFR categories. CKD-EPI 2021 had the second lowest bias across the entire range of GFR after GFR Assessment in Liver disease (6.6 vs. 4.6 mL/min/1.73 m 2 , respectively, p < 0.001). The accuracy of CKD-EPI 2021 was similar to CKD-EPI 2012 (p30 = 67.8% vs. 67.9%, respectively) which was higher than the other equations ( p < 0.001). It had a similar performance in patients with ascites, by diagnoses, Model for End-Stage Liver Disease subgroups, by gender, and in non-Black patients. However, it had a relatively higher overestimation in mGFR ≤ 30 mL/min/1.73 m 2 than most equations (18.5 mL/min/1.73m 2 , p < 0.001). Specifically, 64% of patients with mGFR ≤ 30 mL/min/1.73m 2 were incorrectly classified as a less severe CKD stage by CKD-EPI 2021. In Blacks, CKD-EPI 2021 underestimated eGFR by 17.9 mL/min/1.73 m 2 , which was higher than the alternate equations except for Royal Free Hospital ( p < 0.001). The novel race-neutral eGFR equation, CKD-EPI 2021, improves the GFR estimation overall but may not accurately capture true kidney function in cirrhosis, specifically at low GFR. There is an urgent need for a race-neutral equation in liver disease reflecting the complexity of kidney function physiology unique to cirrhosis, given implications for organ allocation and dual organ transplant.