IU Indianapolis ScholarWorks :: Browsing by Subject "Liver diseases"

Browsing by Subject "Liver diseases"

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Autophagy in liver diseases: A matter of what to remove and whether to keep
(KeAi Communications, 2018-09) Yin, Xiao-Ming; Pathology and Laboratory Medicine, School of Medicine
Bile Acids in Autoimmune Liver Disease: Unveiling the Nexus of Inflammation, Inflammatory Cells, and Treatment Strategies
(MDPI, 2023-11-29) Zhou, Tianhao; Ismail, AbdiGhani; Francis, Heather; Medicine, School of Medicine
As bile acids not solely play an essential role in nutrition absorption, but also in regulating metabolic functions as well as immune response, bile acids and their signaling pathways are increasingly acknowledged as potential therapeutic targets in the context of chronic liver diseases. Bile acid receptors such as G protein bile acid-activated receptor 1 and farnesoid X receptor are expressed in different immune cells engaged in innate immunity. Recently, a series of studies have revealed distinct functions of bile acids and bile acid receptors within the adaptive immune system. In addition, a variety of molecules targeting bile acid receptors and transporters are currently in advanced stages of clinical development. Autoimmune liver diseases including conditions like primary biliary cholangitis, primary sclerosing cholangitis, and autoimmune hepatitis can lead to chronic inflammation, fibrosis, and even cirrhosis and liver failure. In this review, we focus on the role of bile acids in the inflammatory aspects of autoimmune liver diseases.
Comorbidity burden may be associated with increased mortality in patients with severe acute liver injury referred for liver transplantation
(International Scientific Information, Inc., 2020-11-03) Steiner-Temnykh, Lindsey; Dakhoul, Lara; Slaven, James; Nephew, Lauren; Patidar, Kavish R.; Orman, Eric; Desai, Archita P.; Vilar-Gomez, Eduardo; Kubal, Chandrashekhar; Ekser, Burcin; Chalasani, Naga; Chabril, Marwan
Severe acute liver injury (S-ALI) can lead to acute liver and multisystem failure, with high mortality and need for liver transplantation (LT); however, the burden and impact of liver disease and comorbid conditions are unknown.
Contemporary Trends in Hospitalizations for Comorbid Chronic Liver Disease and Substance Use Disorders
(Wolters Kluwer, 2021-06-18) Desai, Archita P.; Greene, Marion; Nephew, Lauren D.; Orman, Eric S.; Ghabril, Marwan; Chalasani, Naga; Menachemi, Nir; Medicine, School of Medicine
Introduction: Chronic liver diseases (CLDs) and substance use disorders (SUDs) are increasingly prevalent and often coexist. Contemporary studies describing the characteristics and hospitalization trends of those with comorbid CLD-SUD are lacking. We aimed to characterize a population-based cohort with comorbid CLD-SUD and describe trends in these hospitalizations over time by individual-level characteristics. Methods: We performed a cross-sectional analysis of the National Inpatient Sample from 2005 through 2017. Diagnosis codes were used to identify adult hospitalizations with CLD, SUD, or both. Bivariate and multivariate analyses were used to make comparisons between diagnosis categories. Unadjusted and age-adjusted trends in these hospitalizations were described over time. Results: Of 401,867,749 adult hospital discharges, 3.2% had CLD-only and 1.7% had comorbid CLD-SUD. Compared with CLD-only, comorbid CLD-SUD hospitalizations resulted in higher inpatient mortality (3.1% vs 2.4%, P < 0.001) and were associated with younger age, male sex, Native American race, and urban and Western US location. Over time, comorbid hospitalizations grew 34%, and the demographics shifted with larger increases in hospitalization rates seen in younger individuals, women, Native Americans, and those publicly insured. In comorbid hospitalizations, alcoholic SUD and CLD decreased, but drug SUDs and nonalcoholic fatty liver diseases are fast-growing contributors. Discussion: In this comprehensive analysis of US hospitalizations, comorbid CLD-SUD hospitalizations are increasing over time and lead to higher inpatient mortality than CLD alone. We further characterize the changing demographics of these hospitalizations, providing a contemporary yet inclusive look at comorbid CLD-SUD hospitalizations. These data can guide interventions needed to improve the poor outcomes suffered by this growing population.
The Dynamic Interplay Between Mast Cells, Aging/Cellular Senescence, and Liver Disease
(Cognizant Communication Corporation, 2020-11) Kundu, Debjyoti; Kennedy, Lindsey; Meadows, Vik; Baiocchi, Leonardo; Alpini, Gianfranco; Francis, Heather; Medicine, School of Medicine
Mast cells are key players in acute immune responses that are evidenced by degranulation leading to a heightened allergic response. Activation of mast cells can trigger a number of different pathways contributing to metabolic conditions and disease progression. Aging results in irreversible physiological changes affecting all organs, including the liver. The liver undergoes senescence, changes in protein expression, and cell signaling phenotypes during aging, which regulate disease progression. Cellular senescence contributes to the age-related changes. Unsurprisingly, mast cells also undergo age-related changes in number, localization, and activation throughout their lifetime, which adversely affects the etiology and progression of many physiological conditions including liver diseases. In this review, we discuss the role of mast cells during aging, including features of aging (e.g., senescence) in the context of biliary diseases such as primary biliary cholangitis and primary sclerosing cholangitis and nonalcoholic fatty liver disease.
Epidemiology of Alcohol-associated Liver Disease
(Elsevier, 2021) Han, Sen; Yang, Zhihong; Zhang, Ting; Ma, Jing; Chandler, Kristina; Liangpunsakul, Suthat; Medicine, School of Medicine
Alcohol-associated liver disease (ALD) is a consequence of excessive alcohol use. It comprises a spectrum of histopathologic changes ranging from simple steatosis, steatohepatitis, and cirrhosis to hepatocellular carcinoma. The public health impact of ALD is growing because of an increase in the prevalence and incidence of ALD in parallel with liver transplant and mortalities. There are multiple factors involved in the pathogenesis and progression of ALD. Reducing alcohol consumption is the cornerstone of ALD management. The efforts to reduce excessive alcohol use at the individual and population levels are urgently needed to prevent adverse outcomes from ALD.
Evaluation of the child with suspected mitochondrial liver disease
(Wiley, 2013) Molleston, Jean P.; Sokol, Ronald J.; Karnsakul, Wikrom; Miethke, Alexander; Horslen, Simon; Magee, John C.; Romero, René; Squires, Robert H.; Van Hove, Johan L. K.; Childhood Liver Disease Research and Education Network (ChiLDREN); Pediatrics, School of Medicine
Four waves of hepatocyte proliferation linked with three waves of hepatic fat accumulation during partial hepatectomy-induced liver regeneration
(Public Library of Science, 2012) Zou, Yuhong; Bao, Qi; Kumar, Sudhanshu; Hu, Min; Wang, Guo-Ying; Dai, Guoli; Biology, School of Science
Partial hepatectomy (PH) triggers hepatocyte proliferation-mediated liver repair and is widely used to study the mechanisms governing liver regeneration in mice. However, the dynamics of the hepatocyte proliferative response to PH remain unclear. We found that PH-induced mouse liver regrowth was driven by four consecutive waves of hepatocyte replication. The first wave exhibited the highest magnitude followed by two moderate waves and one minor wave. Underlying this continuous hepatocyte replication was persistent activation of cell cycle components throughout the period of liver regeneration. Hepatocyte mitotic activity in the first three proliferative cycles showed a circadian rhythm manifested by three corresponding mitosis peaks, which were always observed at Zeitgeber time 0. The Bmal1-Clock/Wee1/Cdc2 pathway has been proposed by others to govern the circadian rhythm of hepatocyte mitosis during liver regeneration. However, we did not observe the correlations in the expression or phosphorylation of these proteins in regenerating livers. Notably, Bmal1 protein displayed frequent changes in hepatic distribution and cellular localization as the liver regrowth progressed. Further, three waves of hepatic fat accumulation occurred during hepatic regeneration. The first started before and lasted through the first round of hepatocyte proliferation, whereas the second and third occurred concomitantly with the second and third mitotic peaks, respectively. Conclusion: PH-induced liver regeneration consists of four continuous waves of hepatocyte proliferation coupled with three waves of hepatic fat accumulation. Bmal1, Wee1, and Cdc2 may not form a pathway regulating the circadian rhythm of hepatocyte mitosis during liver regeneration.
Health care–related transportation insecurity is associated with adverse health outcomes among adults with chronic liver disease
(Wolters Kluwer, 2024-01-11) Ufere, Nneka N.; Lago-Hernandez, Carlos; Alejandro-Soto, Alysa; Walker, Tiana; Li, Lucinda; Schoener, Kimberly; Keegan, Eileen; Gonzalez, Carolina; Bethea, Emily; Singh, Siddharth; El-Jawahri, Areej; Nephew, Lauren; Jones, Patricia; Serper, Marina; Medicine, School of Medicine
Background: Health care-related transportation insecurity (delayed or forgone medical care due to transportation barriers) is being increasingly recognized as a social risk factor affecting health outcomes. We estimated the national burden and adverse outcomes of health care-related transportation insecurity among US adults with chronic liver disease (CLD). Methods: Using the U.S. National Health Interview Survey from 2014 to 2018, we identified adults with self-reported CLD. We used complex weighted survey analysis to obtain national estimates of health care-related transportation insecurity. We examined the associations between health care-related transportation insecurity and health care-related financial insecurity, food insecurity, self-reported health status, work productivity, health care use, and mortality. Results: Of the 3643 (representing 5.2 million) US adults with CLD, 267 [representing 307,628 (6%; 95% CI: 5%-7%)] reported health care-related transportation insecurity. Adults with CLD experiencing health care-related transportation insecurity had 3.5 times higher odds of cost-related medication nonadherence [aOR, 3.5; (2.4-5.0)], 3.5 times higher odds of food insecurity [aOR, 3.5; (2.4-5.3)], 2.5 times higher odds of worsening self-reported health status over the past year [aOR, 2.5; (1.7-3.7)], 3.1 times higher odds of being unable to work due to poor health over the past year [aOR, 3.1; (2.0-4.9)], and 1.7 times higher odds of being in a higher-risk category group for number of hospitalizations annually [aOR, 1.7; (1.2-2.5)]. Health care-related transportation insecurity was independently associated with mortality after controlling for age, income, insurance status, comorbidity burden, financial insecurity, and food insecurity [aHR, 1.7; (1.4-2.0)]. Conclusions: Health care-related transportation insecurity is a critical social risk factor that is associated with health care-related financial insecurity, food insecurity, poorer self-reported health status and work productivity, and increased health care use and mortality among US adults with CLD. Efforts to screen for and reduce health care-related transportation insecurity are warranted.
Heterogeneous liver on research ultrasound identifies children with cystic fibrosis at high risk of advanced liver disease
(Elsevier, 2023) Siegel, Marilyn J.; Leung, Daniel H.; Molleston, Jean P.; Ye, Wen; Paranjape, Shruti M.; Freeman, A. Jay; Palermo, Joseph J.; Stoll, Janis; Masand, Prakash; Karmazyn, Boaz; Harned, Roger; Ling, Simon C.; Navarro, Oscar M.; Karnsakul, Wikrom; Alazraki, Adina; Schwarzenberg, Sarah Jane; Towbin, Alex J.; Alonso, Estella M.; Nicholas, Jennifer L.; Green, Nicole; Otto, Randolph K.; Magee, John C.; Narkewicz, Michael R.; CFLD Network; Pediatrics, School of Medicine
Background: This study examines whether heterogeneous (HTG) pattern on liver ultrasound (US) identifies children at risk for advanced cystic fibrosis liver disease (aCFLD). Methods: Prospective 6-year multicenter case-controlled cohort study. Children with pancreatic insufficient cystic fibrosis (CF) aged 3-12 years without known cirrhosis underwent screening US. Participants with HTG were matched (by age, Pseudomonas infection status and center) 1:2 with participants with normal (NL) US pattern. Clinical status and laboratory data were obtained annually and US bi-annually for 6 years. Primary endpoint was development of nodular (NOD) US pattern consistent with aCFLD. Results: 722 participants underwent screening US, with 65 HTG and 592 NL. Final cohort included 55 HTG and 116 NL with ≥ 1 follow-up US. ALT, AST, GGTP, FIB-4, GPR and APRI were higher, and platelets were lower in HTG compared to NL. HTG had a 9.5-fold increased incidence (95% confidence interval [CI]:3.4, 26.7, p<0.0001, 32.7% vs 3.4%) of NOD versus NL. HTG had a sensitivity of 82% and specificity of 75% for subsequent NOD. Negative predictive value of a NL US for subsequent NOD was 96%. Multivariate logistic prediction model that included baseline US, age, and log(GPR) improved the C-index to 0.90 compared to only baseline US (C-index 0.78). Based on survival analysis, 50% of HTG develop NOD after 8 years. Conclusions: Research US finding of HTG identifies children with CF with a 30-50% risk for aCFLD. A score based on US pattern, age and GPR may refine the identification of individuals at high risk for aCFLD.

Browsing by Subject "Liver diseases"

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