Hepatic Medicine : Evidence and Research最新文献

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.

Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily attacks the respiratory system, other organs, such as the liver, are also affected. In this overview, the effects of SARS-CoV-2 infection on the liver in both healthy people and in those with pre-existing liver disease are documented; the relationship between coronavirus disease 19 (COVID-19) vaccination and liver injury is examined; the mechanism of SARS-CoV-2-associated liver injury is explored; and the long-term consequences of COVID-19 are delineated, both in people with and without pre-existing liver disease.

Purpose: Ethyl glucuronide (EtG), ethyl sulfate (EtS) and phosphatidylethanol (PEth) are considered specific direct biomarkers for detecting alcohol consumption. However, PEth, which is produced in red blood cells (RBC), varies considerably between patients for unknown reasons. We here studied various confounders of PEth elimination including fibrosis after alcohol withdrawal.

Patients and methods: EtG, EtS and PEth together with routine laboratory and clinical parameters were studied in 100 Caucasian heavy drinkers prior and after alcohol detoxification. In addition, fibrosis stage and degree of steatosis were assessed by transient elastography (Fibroscan, Echosens, Paris).

Results: All three biomarkers were highly correlated (0.61-0.72) with initial serum alcohol levels, but only PEth correlated with daily alcohol consumption. After alcohol withdrawal, PEth significantly decreased within 6.1 days from 1708 to 810 ng/mL (half-life varied from 1.6 to 15.2 days). Both levels of serum alcohol but also EtG and EtS were higher in patients with liver cirrhosis as compared to patients without fibrosis despite comparable alcohol consumption suggesting a decreased alcohol elimination in patients with cirrhosis. PEth was also elevated in cirrhosis but not significantly. In contrast, PEth elimination rate was significantly higher in patients with enhanced RBC turnover and signs of alcohol-mediated hemolytic anemia with elevated ferritin, LDH and increased mean corpuscular volume (MCV).

Conclusion: We here demonstrate that alcohol elimination is decreased in patients with liver cirrhosis. In patients with cirrhosis, PEth levels are both affected in opposite directions by enhanced red blood cell turnover and elevated alcohol levels. Our data have important implications for the use and interpretation of PEth in the clinical setting.

Aim: Since 2019, the COVID-19 pandemic wreaked havoc all over the world. Early in the course of the pandemic, multiple hepatic manifestations of COVID-19 were noted. We aim to categorize hepatic dysfunction and its outcome in COVID-19 infection.

Methods: This is a review article based on a literature search in PubMed and Medline databases for articles detailing short-term and long-term outcomes of COVID-19 related liver dysfunction.

Results: The most common hepatic manifestation of COVID-19 was aspartate amino transferase (AST) predominant transaminase elevation. Transaminases improve once the COVID-19 infection resolves. In addition, COVID-19 cholangiopathy, autoimmune hepatitis associated COVID-19, and splanchnic venous thrombosis triggered by COVID-19 are other manifestations. Patients with preexisting liver disease, especially those with cirrhosis, have poor prognosis with COVID-19 infections compared to the general population. Elevations in liver tests were associated with severe COVID-19 infections. Patients with chronic liver disease have a higher risk of morbidity and mortality from COVID-19 infection. Among patients with chronic liver disease, decompensated liver cirrhosis, hepatocellular carcinoma and alcohol-associated liver disease were associated with an increased risk of severity and mortality from COVID-19 infection. Interactions between antiviral therapy for COVID-19 and hepatitis B/hepatitis C medications must be considered in patients with chronic viral hepatitis and COVID-19 infection. COVID-19 vaccination-related hepatic dysfunction has been reported.

Conclusion: COVID-19 is here to stay. Hepatic dysfunction in COVID-19 signals severe COVID-19 infections. Patients with chronic liver disease have higher mortality from COVID-19 than general population. It is important to remember the lessons learned throughout the covid pandemic to take care of patients with COVID-19 now and in the future. Further studies are needed to document long-term outcomes in patients with COVID-19 who developed hepatic dysfunction.

Purpose: In this study, our primary aim is to analyze the genetic expression feature and analyze specific Traditional Chinese medicine (TCM) constitution distribution in non-alcoholic fatty liver disease (NAFLD) and reveal the metabolic characteristic of NAFLD.

Materials and methods: For revealing genetic features, we obtained the gene expression data from the Gene Expression Omnibus (GEO) database of the National Center for Biotechnology Information (NCBI). The genetic data on NAFLD were analyzed by identifying differentially expressed genes (DEGs), associated pathways, co-expressed genetic networks, and gene set enrichment function. Concurrently, we assessed specific constitution distributions among local NAFLD patients through established TCM constitution models and determined the independent variable, including specific constitution to the NAFLD via the regression analyses.

Results: The analyses on GEO datasets showed that simple steatosis in NAFLD is strongly associated with HOMA-insulin resistance (HOMA-IR). Analyses of GEO datasets revealed significantly altered genetic expression profiles between NAFLD and normal populations. For TCM constitution analyses, we demonstrated a decline in yin-yang harmony (YYH) and yang-asthenia (YAAC) constitution, whereas there was an increase in qi-stagnation (QSC) and phlegm-dampness (PDC) in NAFLD. The binary logistic regression analysis indicated that besides other metabolic parameters, YYH, qi asthenia (QAC), YYAC, and yin-asthenia (YAC) were the independent variables of NAFLD, while YAC was the independent variables of T2D. The multilinear regression analyses suggested that NAFLD, DM, BMI, waist, TC, TG, hypertension, ALT, AST, and YAC were the significant determinators of the FPG.

Conclusion: This study presents a relatively comprehensive metabolic profile in steatosis of NAFLD, revealed by significant genetic expression feature alterations and different TCM constitution distribution in NAFLD. Through this method, the study intends to associate the genetic feature with the phenotype of TCM constitution. The results could be applied to assist integrative medicine research in exploring the appropriate personalized approaches for NAFLD.