Liver Injury Research Articles

Turmeric-Induced Liver Injury

Turmeric and its active compound, curcumin, has gained popularity as an herbal supplement due to its anti-inflammatory properties. However, the lack of standardized regulation for herbal supplements raises concerns about potential side effects and toxicity. This case report presents a 53-year-old woman with Behçet disease who developed biopsy-proven drug-induced liver injury (DILI) after initiating a turmeric supplement, with resolution of laboratory abnormalities after a positive supplement de-challenge. This case highlights the importance of noting herbal supplementation during medication reconciliation and underscores the need for rigorous regulatory oversight to ensure the safety of such products.

ZnR/GPR39 regulates hepatic insulin signaling, tunes liver bioenergetics and ROS production, and mitigates liver fibrosis and injury

Adequate supply of zinc is essential for hepatic function and its deficiency is associated with acute liver injury (ALI) and chronic nonalcoholic fatty liver disease (NAFLD). However, how zinc controls hepatic function is unknown. We found that the zinc sensitive ZnR/GPR39, a mediator of zinc signaling, enhances hepatic phosphorylation of ERK1/2, which is reduced in ZnR/GPR39 deficient livers. Surprisingly, livers from ZnR/GPR39 knockout (KO) mice exhibited elevated insulin receptor expression and downstream AKT activation. Moreover, ZnR/GPR39 KO mice had higher blood fasting glucose level, pronounced hepatic lipid accumulation, increased hepatocyte oxygen consumption rate (OCR) and reactive oxygen species (ROS) levels. These data suggest that ZnR/GPR39 modulates insulin receptor signaling, a major pathway in hepatic metabolism. Associated with the impaired signaling, ZnR/GPR39 KO livers exhibited increased tissue fibrosis, manifested by marked elevation of collagen expression, compared to wildtype (WT). Additionally, we found alteration of hepatocyte junctional proteins that was accompanied by increased macrophage infiltration and higher liver inflammation in ZnR/GPR39 KO mice. To determine the role of ZnR/GPR39 in ALI, we applied a mild LPS challenge that induced profound decrease in hepatic OCR, also leading to higher ROS generation in ZnR/GPR39 KO hepatocytes, but not in WT. We further found increased serum IL-2 and AST/ALT ratio only in ZnR/GPR39 KO mice. Our findings reveal a role of ZnR/GPR39 in controlling hepatic insulin receptor signaling and mitigating liver fibrosis and inflammation, thus underscoring the important role of ZnR/GPR39 in liver signaling and function.

AKR7A5 knockout promote acute liver injury by inducing inflammatory response, oxidative stress and apoptosis in mice.

Alcohol liver disease has become a worldwide critical health problem. The ingested alcohol could be converted into acetaldehyde or combined with free fatty acids to induce the endoplasmic reticulum oxidative stress in the liver. Coincidentally, AKR7A5 has both aldehyde detoxification and antioxidant effects. Therefore, we discuss the possible role and mechanism of AKR7A5 in the acute alcohol injury of mice liver. There were four experiment groups, the C57BL/6 mice of wild-type mice (WT) or AKR7A5-/- mice (KO) were intragastrically administrated with saline or 50% ethanol at 14 mL/kg, respectively. Compared to the WT + alcohol group, abnormal liver function, disordered hepatic cord, severe congestion in the hepatic sinus and the space of the hepatic cord, occurrence of oxidative stress, DNA damage and different expressions of apoptosis-related proteins were detected in the KO + alcohol group. Meanwhile, the biological process enrichment analysis showed that the down-regulated proteins were related to the metabolism of fatty acid, the up-regulated proteins positive regulation of reactive oxygen species metabolic process, negative regulation of coagulation and haemostasis. In conclusion, single ethanol binge combined with the absence of AKR7A5 caused more severe inflammatory response, oxidative stress, apoptosis of endogenous pathways, abnormal lipids metabolism and disordered coagulation in mice liver.

Supportive Counselling As A Therapeutic Intervention For Women With Infertility: A Meta-Analysis On Its Role In Mitigating Psychological Trauma And Enhancing Quality Of Life

Supportive Counselling As A Therapeutic Intervention For Women With Infertility: A Meta-Analysis On Its Role In Mitigating Psychological Trauma And Enhancing Quality Of Life

Parentral nutrition associated liver and gut injury is mitigated by a novel dream

Parentral nutrition associated liver and gut injury is mitigated by a novel dream

The prevalence of lifetime trauma and association with physical and psychosocial health among adults at the end of life.

National guidelines recognize lifetime trauma as relevant to clinical care for adults nearing the end of life. We determined the prevalence of early life and cumulative trauma among persons at the end of life by gender and birth cohort, and the association of lifetime trauma with end-of-life physical, mental, and social well-being. We used nationally representative Health and Retirement Study data (2006-2020), including adults age > 50 who died while enrolled (N = 6495). Early life and cumulative traumatic events were measured using an 11-item traumatic events scale (cumulative trauma: 0-5+ events over the lifespan). We included six birth cohorts (born <1924; children of depression [1924-1930]; HRS cohort [1931-1941]; war babies [1942-1947]; early baby-boomers [1948-1953]; mid-baby boomers [1954-1959]). End-of-life outcomes included validated measures of physical (pain, fatigue, dyspnea), mental (depression, life satisfaction), and social (loneliness, social isolation) needs. We report the prevalence of lifetime trauma by gender and birth cohort and the adjusted probability of each end-of-life outcome by trauma using multivariable logistic regression. The mean age at death was 78 years (SD = 11.1) and 52% were female. Lifetime trauma was common (0 events: 19%; 1-2: 47%; 3-4: 25%; 5+: 9%), with variation in individual events (e.g., death of a child, weapons in combat) by gender and birth cohort. After adjustment, increasing cumulative trauma was significantly associated (p-value<0.001) with higher reports of end-of-life moderate-to-severe pain (0 events: 46%; 1-2 events: 50%; 3-4 events: 57%; 5+ events: 60%), fatigue (58%; 60%; 66%; 69%), dyspnea (46%; 51%; 56%; 58%), depression (24%; 33%; 37%; 40%), loneliness (12%; 17%; 19%; 22%), and lower life satisfaction (73%; 63%; 58%; 54%). Older adults in the last years of life report a high prevalence of lifetime traumatic events which are associated with worse end-of-life physical and psychosocial health. A trauma-informed approach to end-of-life care and management of physical and psychosocial needs may improve a patient's quality of life.

Substance use by homeless clinic attenders in Sydney.

Describe patterns of substance use and comorbid conditions among clinic attenders in homeless shelters in Sydney. Retrospective cohort study of 2498 people who attended a psychiatric clinic at one of three homeless hostels between February 2008 and May 2020. Multivariable logistic regression was used to identify factors associated with self-reported substance use, psychiatric diagnosis and measures of social function. A total of 2041 of the 2498 (81.7%) reported the harmful use of at least one substance, with alcohol (61.8%), cannabis (50.9%) and stimulant drugs (34.9%) the three most common. Those reporting the regular use of two or more substances (1466, 58.7%) were more likely to have a history of early life and adult trauma, a diagnosis of personality disorder, a criminal conviction, receive the Disability Support Pension, be chronically homeless and sleep in the open. The study found a high rate of polysubstance use among homeless clinic attenders in Sydney, and an increase in the prevalence of substance use compared to previous studies. Substance use is both a cause and a consequence of homelessness, and services to address substance use have to be part of any program to reduce homelessness and sleeping in the open.

Nebivolol-induced hepatoxicity: a case report

Nebivolol is a third-generation beta-blocker known for its high selectivity for beta-1 adrenergic receptors and its unique ability to induce vasodilation via nitric oxide (NO) release. Nebivolol, despite its favourable safety profile, can lead to significant liver injury. We describe the case of a 73-year-old hypertensive patient who developed significant liver enzyme elevations following the addition of nebivolol to her treatment regimen. Comprehensive workup ruled out other causes, leading to a diagnosis of drug-induced hepatotoxicity. Discontinuation of nebivolol resulted in normalization of liver enzymes. This case underscores the importance of monitoring liver function during beta-blocker therapy, particularly with nebivolol.

S4184 Labetalol and the Liver: A Rare Postpartum Encounter With Drug-Induced Liver Injury

S4184 Labetalol and the Liver: A Rare Postpartum Encounter With Drug-Induced Liver Injury

Utility of Authentic 13C‐Labeled Disaccharide to Calibrate Hyaluronan Content Measurements by LC‐MS

ABSTRACTHyaluronan (hyaluronic acid, HA), a key glycosaminoglycan in the extracellular matrix, plays crucial roles in various physiological and pathological processes, including development, tissue hydration, inflammation, and tumor progression. Traditional methods for HA quantification, such as ELISA‐like assays, often have limitations in sensitivity and specificity, particularly for lower molecular weight HA. In this work, we introduce a coupled liquid chromatographic‐tandem mass spectrometric (LC‐MS/MS) method that employs a chemoenzymatically synthesized 13C‐labeled lyase‐derived authentic HA disaccharide calibrant for quantification of HA at the nanogram level. The method was validated against three HA polysaccharides with the sizes of ~33, 210, and 540 kDa. We applied this quantification technique to mouse tissues and plasma from both healthy and acetaminophen‐induced acute liver injury mice. Our data revealed a ~75‐fold increase in HA concentration in the liver of acetaminophen‐injured mice with a concomitant depletion from plasma. Overall, our method offers a robust, universal, and highly sensitive tool for HA analysis in diverse biological samples that will advance the investigation of the roles of this polysaccharide in human disease conditions.

S4610 Unorthodox Alcoholic Liver Injury

S4610 Unorthodox Alcoholic Liver Injury

S4431 A Severe Case of Drug-Induced Liver Injury After Ingestion of Amoxicillin-Clavulanic Acid

S4431 A Severe Case of Drug-Induced Liver Injury After Ingestion of Amoxicillin-Clavulanic Acid

A traditional medicinal food &lt;i&gt;Arum rupicola&lt;/i&gt; (Kardeh) ameliorates thioacetamide-induced hepatotoxicity in animal model: Role of PCNA/Bax, oxidative stress, and inflammatory cytokines

Nutraceuticals are major contributors to human health because of their modulatory effects on various physiological and pathological processes. Arum rupicola (Kardeh) is a traditional medicinal food used for many gastrointestinal and enzymatic disorders. The present study evaluates the acute toxicity and hepatoprotective effects of methanolic extracts of Arum rupicola (MEAR) in rat with thioacetamide (TAA)-induced liver injury in rat. Thirty Sprague-Dawley rats were divided into five groups: Group A, normal control, and group B, TAA control groups were treated orally with 10% tween 20; group C reference rat received daily of 50 mg/kg silymarin drug; Groups D and E rat received daily doses of 250 mg/kg and 500 mg/kg MEAR, respectively. In addition, group B–E received three injections of 200 mg/kg TAA weekly for 60 days. The safety evaluation of MEAR revealed nontoxic effects at 2,000 and 5,000 mg/kg dosage in rat. TAA inoculation provoked significant hepatotoxic alterations indicated by increased hepatocyte proliferation, endothelial tissue injury, ambiguous nucleus, and elevated cytoplasmic vacuoles. TAA treatment initiated increased inflammatory response and necrosis process in different areas of hepatic tissues. Meanwhile, MEAR treatment showed significant prophylaxis against TAA-induced hepatotoxicity, supported by its suppressing actions on oxidative stress, and apoptotic and inflammatory mediators. MEAR treatment significantly down-regulated proliferating cell nuclear antigen (PCNA) in both liver and spleen parenchymal tissues, lowered pro-apoptotic Bcl-2-associated X (Bax) proteins, reduced inflammatory and redox mediators, lowered transforming growth factor-beta tissue expression and malondialdehyde content, while, increased antioxidants (superoxide dismutase, catalase, and glutathione peroxidase). The outcomes provided significant hepatoprotective potential of MEAR mediated by its modulatory effects on several cellular pathways, making it a viable source of a potent pharmaceutical discovery.

Increased attention to women with drug-induced liver injury: Risk factors and early intervention

A recent study by Yu-Ting and colleagues has unveiled the clinical characteristics and risk factors of acute drug-induced liver injury (DILI). Upon reading the article, we found that there are some differences between female and male patients with DILI in terms of clinical and pathological features, especially in the number of patients, the degree of liver inflammation, and the risk of autoimmune liver disease. Therefore, it is necessary to pay attention to female patients with DILI and their outcomes, and to intervene appropriately in advance. This article analyzes the reasons for the differences between female and male patients with DILI and makes recommendations for patient prognosis.

7023 Hypoinsulinemic Hypoglycemia in a Severely Malnourished Patient with an Acute Liver Injury: A Marker of Poor Outcome!

7023 Hypoinsulinemic Hypoglycemia in a Severely Malnourished Patient with an Acute Liver Injury: A Marker of Poor Outcome!

S4536 The Use of N-Acetylcysteine (NAC) in Cocaine-Induced Acute Liver Injury: A Case Report

S4536 The Use of N-Acetylcysteine (NAC) in Cocaine-Induced Acute Liver Injury: A Case Report

S1939 The Evolving Landscape of Drug Induced Liver Injury (DILI): Tracking New Drug Culprits

S1939 The Evolving Landscape of Drug Induced Liver Injury (DILI): Tracking New Drug Culprits

S4489 Too Much of a Good Thing? Kombucha-Induced Liver Injury

S4489 Too Much of a Good Thing? Kombucha-Induced Liver Injury

S4396 Complexities of Managing Chronic Hepatitis B in HIV: A Case of Acute Liver Injury Post-Medication Change

S4396 Complexities of Managing Chronic Hepatitis B in HIV: A Case of Acute Liver Injury Post-Medication Change

S4504 Ribavirin Treatment in Acute HEV-Induced Liver Injury in a Healthy US Female: A Case Report

S4504 Ribavirin Treatment in Acute HEV-Induced Liver Injury in a Healthy US Female: A Case Report