Hepatic Medicine : Evidence and Research最新文献

Purpose: Thyroid-stimulating hormone (TSH) has been identified as an independent risk factor for non-alcoholic fatty liver disease (NAFLD), TSH binds to the TSH receptor (TSHR) to exert its function. However, the underlying mechanisms by which TSHR influences NAFLD development remain unclear. This study investigates the role of miR374b in NAFLD progression.

Methods: Firstly, a rat model of non-alcoholic fatty liver was constructed and divided into a normal group and a model group. The liver tissue pathology and fat accumulation were detected by Oil Red O staining and hematoxylin-eosin staining. Western blot and Real time PCR were used to detect for the impact of TSHR/miR-374b/C/EBP β/ FoxO1 pathway in the NAFLD model, and the expression of relevant inflammatory factors in each group was detected by ELISA assay. A NAFLD cell model was constructed using HepG2 cells, TSHR overexpression and interference, combined with miR-374b inhibitor and mimics, were transfected simultaneously to demonstrate TSHR/miR-374b/C/EBP β/ The mechanism of FoxO1 adipogenesis in vitro.

Results: TSHR stimulates miR374b secretion in human liver cancer cells (HepG2) and promotes lipid accumulation in the liver. Deficiency of miR374b in HepG2 cells attenuated NAFLD progression. Mechanistically, TSH increases miR374b expression, which then suppresses the transcription of its target genes, CCAAT/enhancer binding protein-b (C/EBP β) and Forkhead Box Protein O1 (FOXO1). This suppression influences the expression of downstream lipid metabolism proteins, including PPARγ, SREBP2, and SREBP1c. Additionally, miR374b directly targets the 3'UTR of C/EBP β and FOXO1, establishing a negative feedback loop in lipid metabolism.

Conclusion: These findings suggest that TSHR-induced upregulation of miR374b accelerates NAFLD progression by modulating lipid metabolism pathways through C/EBP β and FOXO1.

Background: Thyrotoxicosis is often associated with abnormal liver tests. This study aimed to characterize the clinical features and laboratory findings in thyrotoxic patients with liver abnormalities and to identify predictive factors for differentiating thyroid storm within this population.

Methods: This is a retrospective review of thyrotoxic patients with hepatic dysfunction between January 2015, and January 2021, at Siriraj Hospital, Thailand. Univariate and multivariate analyses were performed to identify the factors associated with thyroid storm.

Results: Among 771 thyrotoxic patients, 43 revealed abnormal liver tests within six months of diagnosis (5.58%). The mean age was 53.16 ± 15.10 years, with a female predominance (60.5%), and the majority (97.7%) were diagnosed with Graves' disease. The most common comorbidities were atrial fibrillation, heart failure, and dyslipidemia. Hepatic dysfunction presented as non-specific, with 46.5% showing a cholestatic pattern, 30.2% a mixed pattern, and 20.9% a hepatocellular pattern. The most possible etiologies of hepatic dysfunction were hyperthyroidism-related hepatitis (41.9%) with atrial fibrillation with congestive hepatopathy (38.9%), concomitant with chronic hepatitis C infection (14.0%), and methimazole-induced hepatic dysfunction (9.3%). The younger age, congestive heart failure, and total bilirubin levels ≥ 3.0 mg/dL were independent factors in distinguishing clinical thyroid storm among thyrotoxic patients without thyroid storm.

Conclusion: Liver abnormalities can be observed in patients with thyrotoxicosis. The possible causes are multifactorial, including hyperthyroidism-related hepatitis, atrial fibrillation with congestive hepatopathy, and chronic hepatitis C infection. Younger age, congestive heart failure, and total bilirubin ≥ 3.0 mg/dL were predictive factors for thyroid storm diagnosis among thyrotoxic patients.

Purpose: Both hepatic iron accumulation and hemolysis have been identified as independent prognostic factor in alcohol-related liver disease (ALD); however, the mechanisms still remain poorly understood. We here demonstrate that hepatocytes are able to directly ingest aged and ethanol-primed red blood cells (RBCs), a process termed efferocytosis.

Methods: Efferocytosis of RBCs was directly studied in vitro and observed by live microscopy for real-time visualization. RBCs pretreated with either CuSO₄ or ethanol following co-incubation with Huh7 cells and murine primary hepatocytes. Heme oxygenase-1 (HO-1) and other targets were measured by q-PCR.

Results: As shown by live microscopy, oxidized RBCs, but not intact RBCs, are rapidly ingested by both Huh7 cells and murine primary hepatocytes within 10 minutes. In some cases, more than 10 RBCs were seen within hepatocytes, surrounding the nucleus. RBC efferocytosis also rapidly induces HO1, its upstream regulator Nuclear factor erythroid 2-related factor 2 (Nrf2) and ferritin, indicating efficient heme degradation. Preliminary data further suggest that hepatocyte efferocytosis of oxidized RBCs is, at least in part, mediated by scavenging receptors such as ASGPR1. Of note, pretreatment of RBCs with ethanol but also heme and bilirubin also initiated efferocytosis. In a cohort of heavy human drinkers, a significant correlation of hepatic ASGPR1 with the heme degradation pathway was observed.

Conclusion: We here demonstrate that hepatocytes can directly ingest and degrade oxidized RBCs through efferocytosis, a process that can be also triggered by ethanol, heme and bilirubin. Our findings are highly suggestive for a novel mechanism of hepatic iron overload in ALD patients.

Background and aims: Real-world analyses on burden of illness in patients with alpha-1 antitrypsin deficiency (AATD) are limited. We investigated the real-world burden of liver-related clinical events among adult and pediatric patients with AATD in the USA.

Methods: This was a retrospective, observational analysis of administrative claims data from the IQVIA PharMetrics^® Plus and Ambulatory Electronic Medical Records databases from 2011 to 2022. Patients had a diagnosis of liver and/or lung disease with ≥180 days of continuous enrollment in the IQVIA PharMetrics Plus database before and ≥90 days after their first diagnosis. Follow-up time was assigned to the AATD with liver disease health state or AATD with both liver and lung disease health state (for patients aged ≥18 years only). Baseline demographic characteristics and liver-related clinical events of interest were reported.

Results: Of 5136 eligible patients, 771 adult and 123 pediatric patients contributed time to the AATD with liver disease health state; 541 adults contributed time to the AATD with both liver and lung disease health state. Among adults, patients with both liver and lung disease had higher rates of liver-related clinical events than patients with liver disease alone. Ascites was the most frequently observed clinical event among adults in both health states, and the median time to the composite of any liver-related clinical event was 26.5 days among all adults combined. Across all pediatric age groups, ascites, gastrointestinal bleed and hepatic encephalopathy were more common than spontaneous bacterial peritonitis and hepatocellular carcinoma, but median time to liver-related clinical event varied by age group at index date and type of event. No liver transplantations occurred in patients aged 6-17 years.

Conclusion: Diagnosed AATD with liver disease carries a substantial burden on adult and pediatric patients; new treatment options are warranted to avoid disease progression to decompensating events.

Orthotopic liver transplantation (OLT) currently serves as the sole definitive treatment for thousands of patients suffering from end-stage liver disease; and the existing supply of donor livers for OLT is drastically outpaced by the increasing demand. To alleviate this significant gap in treatment, several experimental approaches have been devised with the aim of either offering interim support to patients waiting on the transplant list or bioengineering complete livers for OLT by infusing them with fresh hepatic cells. Recently, interspecies blastocyst complementation has emerged as a promising method for generating complete organs in utero over a short timeframe. When coupled with gene editing technology, it has brought about a potentially revolutionary transformation in regenerative medicine. Blastocyst complementation harbors notable potential for generating complete human livers in large animals, which could be used for xenotransplantation in humans, addressing the scarcity of livers for OLT. Nevertheless, substantial experimental and ethical challenges still need to be overcome to produce human livers in larger domestic animals like pigs. This review compiles the current understanding of interspecies blastocyst complementation and outlines future possibilities for liver xenotransplantation in humans.

Background and aims: Hepatic encephalopathy (HE) is characterized by neuropsychiatric manifestations in patients with decompensated cirrhosis (DC) and/or liver failure. This study aimed to investigate the predictive value of thyroid hormone in patients with HE.

Methods: Patients with DC and HE were enrolled, and multivariate logistic analysis was conducted to analyze the risk factors for 1-year mortality.

Results: Among the 81 patients with HBV-related DC and HE, 9 (11.1%) died within 3 months, and 15 (18.5%) died within the first year. More patients with FT3 < 3.5pmol/L had ascites (33.3% vs 8.9%, P<0.01) and higher model for end-stage liver disease (MELD) (Z=3.669, P<0.01). Additionally, free triiodothyronine (FT3) levels were lower in the non-survivor group (P<0.01). FT3 exhibited a negative correlation with international normalized ratio and MELD (both P<0.05). Multivariate analysis revealed that FT3, gamma-glutamyl transpeptidase (GGT), and spontaneous bacterial peritonitis (SBP) were independent risk factors for 1-year mortality of HE. A new model incorporating FT3, GTT, and SBP demonstrated superiority to MELD based on the AUROC (0.9 and 0.752, P=0.04).

Conclusion: Low FT3, but not thyroid-stimulating hormone and free tetraiodothyronine, was identified as an independent risk factor for 1-year mortality in patients with DC and HE. The newly proposed prognostic model, which includes FT3, GTT, and SBP, holds significant predictive value.

Purpose: In Ethiopia, most people rely heavily on traditional therapeutic plants that have been used for years. The practice of traditional medicines use to treat hepatitis is currently gaining popularity due to the limited availability and affordability of modern drugs. The aim of this study was, therefore, to assess the traditional medicinal plants use to treat viral hepatitis among communities of Central region of Ethiopia.

Methods: Data was collected from November 2018 to December 2021 in Central Ethiopia. An open-ended semi-structured interview was used among purposively selected herbalists, traditional medicine entrepreneurs, village heads, and patients visiting traditional healers for hepatitis treatments. A 5 mL blood sample was collected from patients who visited a traditional healers' clinic for hepatitis treatment and tested for HBsAg and HCV-antibody by using ELISA. Among HBsAg-positives, further nucleic acid test for HBV-DNA load was assessed to measure the effects of prescribed medicinal plants.

Results: Herbalists cited 24 plants that were used for hepatitis treatment; of which Rumex nepalensis, Vangueria apiculata, and Solanum incanum were the most frequently cited plants. Remedies were commonly prepared by crushing or powdering, mixing them with water, and taken orally. Forty-two individuals were diagnosed and treated as hepatitis patients by herbalists, of which eight of them were HBsAg-positive but no positives for anti-HCV ELISA. At the third and sixth months of viral load assessment among HBsAg-positive, serum HBV-DNA suppression was observed in three individuals treated with different combinations of frequently cited plants.

Conclusion: In this study, traditional healers used various plants to treat hepatitis. HBV-DNA suppressive activity was detected in three NAT-positive individuals who were treated by using a mixture of these frequently cited and highest preference-ranked plants. This suggests that these plants have antiviral properties and serve as a basis for more pharmacological research in the quest for new antiviral agents.

Purpose: Hepatocellular carcinoma (HCC) is a prevalent form of cancer that is distributed globally. Disulfidptosis, characterized by the fragility of the actin cytoskeleton, represents a distinct type of cell death and holds promise for novel cancer therapies. Nevertheless, the connection among disulfidptosis-associated long non-coding RNAs (lncRNAs) and HCC is still unexplored. This study uses an in silico approach to provide the novel biomarkers of disulfidptosis-associated lncRNAs for predicting the immune response and prognosis with HCC.

Methods: In order to address this gap, we integrated transcriptomic data of HCC from The Cancer Genome Atlas (TCGA) and identified genes that exhibit differential expression with disulfidptosis and lncRNAs. Through co-expression analysis, we identified disulfidptosis-related lncRNAs. Afterwards, by employing univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO), a model for disulfidptosis-associated lncRNA was constructed. The risk model underwent assessment through the utilization of diverse analytical methodologies, including functional enrichment annotation, Kaplan-Meier analysis, principal component analysis (PCA), immune infiltration and immune status analysis, as well as tumor mutation analysis. Furthermore, we discussed the implications of the model in predicting drug sensitivity.

Results: Our study culminated in the construction of a disulfidptosis-related lncRNA model comprising four prognostic disulfidptosis-related lncRNAs (ACYTOR, NRAV, AL080248.1, and AC069307.1). This model demonstrates exceptional diagnostic value for HCC patients and holds practical implications for guiding clinicians in personalizing immunotherapy and drug selection based on individual variations.

Conclusion: In summary, our research introduces a novel predictive tool utilizing disulfidptosis-related lncRNAs, offering potential guidance for the therapeutic management of HCC.

Background: This study describes the epidemiological pattern of acute hepatitis B virus (HBV) infection in Saudi Arabia from 2006 to 2021. It explores case frequency and the crude incidence rate (CIR) by year of diagnosis, age group, region, gender, and nationality of patients.

Methods: Retrospective data on acute hepatitis B cases diagnosed across 20 regions of Saudi Arabia during January 2006 to December 2021 were obtained from the Saudi Ministry of Health's Statistical Yearbook. Statistical analyses were conducted using SPSS version 20.0, employing both parametric and non-parametric tests.

Results: The highest CIR was reported in the regions of Qunfudah, Jeddah, Tabuk, and Taif (28.6, 25.2, 25.1, and 23.4 per 100,000 people). In contrast, the lowest CIR was documented in the regions of Hail, Qurayyat, Jouf, and Hafr AL-Baten (3.6, 3.5, 2.9, and 1.2 per 100,000 people). Incidence rates were notably elevated in those aged 45 years and above (30.6 per 100,000 individuals), followed by the 15-44 age group (14.2 per 100,000 individuals), and were lowest in children aged 0-14 years (0.8 per 100,000 individuals). Regarding gender differences, HBV infection rates were 1.4 times higher in Saudi males than females and 2.2 times higher in non-Saudi males compared to females. Overall, Saudi nationals had a 4.2 times higher HBV infection rate than non-Saudis during the study period.

Conclusion: This study highlights diverse acute Hepatitis B infection rates across Saudi regions, with higher rates in Qunfudah, Jeddah, Tabuk, and Taif, and lower rates in Hail, Qurayyat, Jouf, and Hafr AL-Baten. Predominance among ages 45+, followed by 15-44, and lowest in 0-14 age groups was observed. Gender variations showed notably higher rates in Saudi and non-Saudi males. The notably higher prevalence among Saudi nationals implies key considerations for public health strategies.