Browsing by Subject "Chronic liver disease"
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Item Bile Acid Receptor Therapeutics Effects on Chronic Liver Diseases(Frontiers Media, 2020-01-29) Meadows, Vik; Kennedy, Lindsey; Kundu, Debjyoti; Alpini, Gianfranco; Francis, Heather; Medicine, School of MedicineIn the past ten years, our understanding of the importance of bile acids has expanded from fat absorption and glucose/lipid/energy homeostasis into potential therapeutic targets for amelioration of chronic cholestatic liver diseases. The discovery of important bile acid signaling mechanisms, as well as their role in metabolism, has increased the interest in bile acid/bile acid receptor research development. Bile acid levels and speciation are dysregulated during liver injury/damage resulting in cytotoxicity, inflammation, and fibrosis. An increasing focus to target bile acid receptors, responsible for bile acid synthesis and circulation, such as Farnesoid X receptor and apical sodium-dependent bile acid transporter to reduce bile acid synthesis have resulted in clinical trials for treatment of previously untreatable chronic liver diseases such as non-alcoholic steatohepatitis and primary sclerosing cholangitis. This review focuses on current bile acid receptor mediators and their effects on parenchymal and non-parenchymal cells. Attention will also be brought to the gut/liver axis during chronic liver damage and its treatment with bile acid receptor modulators. Overall, these studies lend evidence to the importance of bile acids and their receptors on liver disease establishment and progression.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 Consensus: guidelines: best practices for detection, assessment and management of suspected acute drug-induced liver injury during clinical trials in patients with nonalcoholic steatohepatitis(Wiley, 2019-03) Regev, Arie; Palmer, Melissa; Avigan, Mark I.; Dimick‐Santos, Lara; Treem, William R.; Marcinak, John F.; Seekins, Daniel; Krishna, Gopal; Anania, Frank A.; Freston, James W.; Lewis, James H.; Sanyal, Arun J.; Chalasani, Naga; Gastroenterology, IU School of MedicineBACKGROUND: The last decade has seen a rapid growth in the number of clinical trials enrolling patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH). Due to the underlying chronic liver disease, patients with NASH often require different approaches to the assessment and management of suspected drug-induced liver injury (DILI) compared to patients with healthy livers. However, currently no regulatory guidelines or position papers systematically address best practices pertaining to DILI in NASH clinical trials. AIMS: This publication focuses on best practices concerning the detection, monitoring, diagnosis and management of suspected acute DILI during clinical trials in patients with NASH. METHODS: This is one of several papers developed by the IQ DILI Initiative, comprised of members from 15 pharmaceutical companies, in collaboration with DILI experts from academia and regulatory agencies. This paper is based on extensive literature review, and discussions between industry members with expertise in drug safety and DILI experts from outside industry to achieve consensus on common questions related to this topic. RESULTS: Recommended best practices are outlined pertaining to hepatic inclusion and exclusion criteria, monitoring of liver tests, DILI detection, approach to a suspected DILI signal, causality assessment and hepatic discontinuation rules. CONCLUSIONS: This paper provides a framework for the approach to assessment and management of suspected acute DILI during clinical trials in patients with NASH.Item Drug‐Induced Liver Injury in Patients With Chronic Liver Disease(Wiley, 2025) Ghabril, Marwan; Vuppalanchi, Raj; Chalasani, Naga; Medicine, School of MedicineObjective: Drug-induced liver injury (DILI) is a global problem and can develop from exposure to prescription or over-the-counter medications as well as herbal and dietary supplements. The diagnosis of DILI is clinically challenging, and liver injury can be severe leading to liver failure, death, or liver transplantation. Patients with underlying chronic liver diseases (CLD) may be at increased risk for DILI, which is associated with factors related to drug or liver disease. Methods: This review summarises current knowledge on the risk and outcomes of DILI in patients with CLD. Results: Patients with CLD may be at an increased risk for DILI. Additionally patients with underlying CLD are at risk for more severe liver injury and worse outcomes after DILI. Discussion: The risk for and poor outcomes from DILI are accentuated in patients with CLD and potentially leading to the worst-case scenario of acute-on-chronic liver failure. We highlight the key observations on DILI with a broad range of underlying liver diseases and the high-DILI risk agents implicated in those populations.Item Health-related quality of life is dynamic in alcohol hepatitis and responds to improvement in liver disease and alcohol consumption(Wiley, 2022) Madathanapalli, Abhishek; Tang, Qing; Lammert, Craig; Samala, Niharika; Shah, Vijay H.; Sanyal, Arun; Chalasani, Naga; Desai, Archita P.; Biostatistics, School of Public HealthBackground: The impact of alcoholic hepatitis (AH) on health-related quality of life (HRQOL) remains inadequately described. We aimed to characterize HRQOL in AH and heavy drinkers (HD), and its associations with clinical variables and outcomes. Methods: This is a post hoc analysis of participants in the Translational Research and Evolving Alcoholic Hepatitis Treatment 001 study (NCT02172898). HRQOL was measured using Short Form Health Survey (SF-36). Mean SF-36 scores were compared in AH and HD with two-sample t-tests. Associations among clinical characteristics, 30-day mortality, and SF-36 mental and physical component scores (MC, PC) were investigated with generalized linear and logistic multivariate regression models. Trends of MC and PC scores were analyzed using one-way ANOVA. Results: Participants with AH (n = 258) and HD (n = 181) were similar demographically. AH cases had a mean Model for End-stage Liver Disease (MELD) score of 23 (7). AH cases had lower PC scores [37 (10) vs. 48 (11), p < 0.001] but higher MC scores [37 (13) vs. 32 (13), p < 0.001]. MC scores were independently associated with age, male gender, and daily alcohol consumption; PC scores were independently associated with age, BMI, alanine aminotransferase concentration, alkaline phosphatase concentration, white blood cell counts, and the presence of ascites. With each 5-point decrease in the baseline PC score, the adjusted odds of dying within 30 days increased by 26.7% (95% CI 1% to 46%). Over time, HRQOL in AH improved (day 0 to day 180 delta PC score: 4.5 ± 1.7, p = 0.008; delta MC score: 9.8 ± 2.0, p < 0.001). Participants with a MELD score <15 by day 180 had greater increases in PC scores than those with MELD score ≥15 (delta PC score 7.1 ± 1.8 vs. -0.7 ± 2.3, p = 0.009), while those abstinent by day 180 had greater increases in MC scores than those who were not abstinent (delta MC score 9.1 ± 1.8 vs. 2.8 ± 2.4, p = 0.044). Conclusions: HRQOL is poor in AH and HD in a domain-specific pattern. Independent of MELD score, lower baseline HRQOL is associated with higher 30-day mortality. Over time, HRQOL improves with greater gains seen in individuals with improved MELD scores and those who were abstinent.Item Increased mortality from alcohol use disorder, alcohol-associated liver disease, and liver cancer from alcohol among older adults in the United States: 2000 to 2021(Wiley, 2025) Danpanichkul, Pojsakorn; Duangsonk, Kwanjit; Tham, Ethan Kai Jun; Tothanarungroj, Primrose; Auttapracha, Thanida; Prasitsumrit, Vitchapong; Sim, Benedix; Tung, Daniel; Barba, Romelia; Wong, Robert J.; Leggio, Lorenzo; Yang, Ju Dong; Chen, Vincent L.; Noureddin, Mazen; Díaz, Luis Antonio; Arab, Juan Pablo; Wijarnpreecha, Karn; Liangpunsakul, Suthat; Medicine, School of MedicineBackground: To investigate the trends in alcohol-associated liver disease (ALD), liver cancer from alcohol, and alcohol use disorder (AUD) burden among older adults in the United States (US). Methods: We gathered the ALD, liver cancer from alcohol, and AUD prevalence, mortality, and age-standardized rates (ASRs) from the Global Burden of Disease (GBD) Study 2021 between 2010 and 2021. We estimated the annual percent change (APC) with confidence intervals (CIs) for the burden of ALD, liver cancer from alcohol, and AUD in older adults (>70 years) in the United States. The findings were contrasted with global estimates and categorized by sex and state. Results: In 2021, there were approximately 512,340 cases of AUD, 56,990 cases of ALD, and 4490 cases of primary liver cancer from alcohol among older adults in the United States. In contrast to declining ASRs of prevalence and mortality in the global burden, these parameters were increased in older adults in the United States. From 2000 to 2021, prevalence from AUD (APC: 0.54%, 95% CI 0.43% to 0.65%), ALD (APC + 0.54%, 95% CI 0.22% to 0.86%), and primary liver cancer from alcohol (APC 2.93%, 95% CI 2.76% to 3.11%) increased. Forty states in the United States exhibited a rise in the prevalence rates of ALD in older adults. Conclusion: Our findings highlighted the increased prevalence and mortality of AUD, ALD, and primary liver cancer from alcohol among older adults in the United Sates, contrasting with the decline in global trends. Public health strategies on ALD, AUD, and primary liver cancer from alcohol, which targets older adults, are urgently needed.Item Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study(Elsevier, 2018-05) Ng, Vicky L.; Sorensen, Lisa G.; Alonso, Estella M.; Fredericks, Emily M.; Ye, Wen; Moore, Jeff; Karpen, Saul J.; Shneider, Benjamin L.; Molleston, Jean P.; Bezerra, Jorge A.; Murray, Karen F.; Loomes, Kathleen M.; Rosenthal, Philip; Squires, Robert H.; Wang, Kasper; Arnon, Ronen; Schwarz, Kathleen B.; Turmelle, Yumirle P.; Haber, Barbara H.; Sherker, Averell H.; Magee, John C.; Sokol, Ronald J.; Pediatrics, School of MedicineOBJECTIVES: To assess neurodevelopmental outcomes among participants with biliary atresia with their native liver at ages 12 months (group 1) and 24 months (group 2), and to evaluate variables predictive of neurodevelopmental impairment. STUDY DESIGN: Participants enrolled in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with either the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition. Scores (normative mean = 100 ± 15) were categorized as ≥100, 85-99, and <85 for χ2 analysis. Risk for neurodevelopmental impairment (defined as ≥1 score of <85 on the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition, scales) was analyzed using logistic regression. RESULTS: There were 148 children who completed 217 Bayley Scales of Infant and Toddler Development, 3rd edition, examinations (group 1, n = 132; group 2, n = 85). Neurodevelopmental score distributions significantly shifted downward compared with test norms at 1 and 2 years of age. Multivariate analysis identified ascites (OR, 3.17; P = .01) and low length z-scores at time of testing (OR, 0.70; P < .04) as risk factors for physical/motor impairment; low weight z-score (OR, 0.57; P = .001) and ascites (OR, 2.89; P = .01) for mental/cognitive/language impairment at 1 year of age. An unsuccessful hepatoportoenterostomy was predictive of both physical/motor (OR, 4.88; P < .02) and mental/cognitive/language impairment (OR, 4.76; P = .02) at 2 years of age. CONCLUSION: Participants with biliary atresia surviving with native livers after hepatoportoenterostomy are at increased risk for neurodevelopmental delays at 12 and 24 months of age. Those with unsuccessful hepatoportoenterostomy are >4 times more likely to have neurodevelopmental impairment compared with those with successful hepatoportoenterostomy. Growth delays and/or complications indicating advanced liver disease should alert clinicians to the risk for neurodevelopmental delays, and expedite appropriate interventions.Item A Primer to the Diagnostic and Clinical Utility of Spleen Stiffness Measurement in Patients With Chronic Liver Disease(Wolters Kluwer, 2022-01-28) Mladenovic, Andrea; Vuppalanchi, Raj; Desai, Archita P.; Medicine, School of MedicineItem PROMIS Profile-29 is a valid instrument with distinct advantages over legacy instruments for measuring quality of life in chronic liver disease(Wolters Kluwer, 2023-12) Desai, Archita P.; Madathanapalli, Abhishek; Tang, Qing; Orman, Eric S.; Lammert, Craig; Patidar, Kavish R.; Nephew, Lauren D.; Ghabril, Marwan; Monahan, Patrick O.; Chalasani, Naga; Medicine, School of MedicineBackground and Aims: The Patient-Reported Outcomes Measurement Information System (PROMIS) is increasingly used to measure health-related quality of life, yet, it has not been well-studied in chronic liver disease (CLD). This study compares PROMIS Profile-29 to Short-Form Health Survey (SF-36) and Chronic Liver Disease Questionnaire (CLDQ) in patients with CLD. Approach and Results: In all, 204 adult outpatients with CLD completed PROMIS-29, CLDQ, SF-36 and usability questionnaires. Mean scores were compared between groups, the correlation between domain scores was assessed, and floor/ceiling effects were calculated. Etiologies of CLD were NAFLD (44%), hepatitis C (16%), and alcohol (16%). Fifty-three percent had cirrhosis and 33% were Child-Pugh B/C with a mean model for end-stage liver disease score of 12.0. In all 3 tools, the poorest scores were in physical function and fatigue. The presence of cirrhosis or complications was associated with worse scores in most PROMIS Profile-29 domains, indicating known group validity. Strong correlations (r ≥ 0.7) were present between Profile-29 and SF-36 or CLDQ domains measuring similar concepts, indicating strong convergent validity. Profile-29 was completed faster than SF-36 and CLDQ (5.4 ± 3.0, 6.7 ± 3.3, 6.5 ± 5.2 min, p = 0.003) and rated equally on usability. All CLDQ and SF-36 domains reached the floor or ceiling, while none were noted for Profile-29. These floor/ceiling effects were magnified when assessed in those with and without cirrhosis, indicating the improved depth of measurement by Profile-29. Conclusions: Profile-29 is a valid, more efficient, well-received tool that provides an improved depth of measurement when compared to SF-36 and CLDQ and, therefore, an ideal tool to measure general health-related quality of life in CLD.Item Real-world effectiveness of COVID-19 vaccination in liver cirrhosis: a systematic review with meta-analysis of 51,834 patients(Taylor & Francis, 2023-01-17) Beran, Azizullah; Mhanna, Asmaa; Mhanna, Mohammed; Hassouneh, Ramzi; Abuhelwa, Ziad; Mohamed, Mouhand F. H.; Sayeh, Wasef; Musallam, Rami; Assaly, Ragheb; Abdeljawad, Khaled; Medicine, School of MedicineSARS-CoV-2 vaccinations were found to be highly effective in phase 3 clinical trials. However, these trials have not reported data regarding the subgroup of liver disease or excluded patients with liver disease. The effectiveness of COVID-19 vaccines among liver cirrhosis (LC) patients is unclear. We conducted this meta-analysis to assess the effectiveness of SARS-CoV-2 vaccination in LC patients. A comprehensive literature search was conducted to include all the relevant studies that compared the outcomes of LC patients who received SARS-CoV-2 vaccines vs. unvaccinated patients. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated by the Mantel-Haenszel method within a random-effect model. Four studies with 51,834 LC patients (20,689 patients received at least one dose vs 31,145 were unvaccinated) were included. COVID-19–related complications, including hospitalization (RR 0.73, 95% CI 0.59–0.91, P = 0.004), mortality (RR 0.29, 95% CI 0.16–0.55, P = 0.0001), and need for invasive mechanical ventilation (RR 0.29, 95% CI 0.11–0.77, P = 0.01), were significantly lower in the vaccinated group compared to the unvaccinated group. SARS-CoV-2 vaccination in LC patients reduced COVID-19–related mortality, intubation, and hospitalization. SARS-CoV-2 vaccination is highly effective in LC. Further prospective studies, preferably randomized controlled trials, are necessary to validate our findings and determine which vaccine is superior in patients with LC.