Biomarkers For Liver Disease Research Articles

Persistent organic pollutants associate with liver disease in a Finnish general population sample.

Persistent organic pollutants (POPs) have multiple adverse effects on human health. Recent studies show a possible association with liver disease, but population-based data are scarce. In this population-based study, we studied the associations between POPs and biomarkers of liver disease and incident liver disease. This study consisted of 2789 adults that participated in the environmental toxin subset of the Finnish health-examination survey, FINRISK 2007. Toxins were measured from serum samples, and standard liver tests and dynamic aspartate aminotransferase-alanine aminotransferase ratio (dAAR) were measured as biomarkers of liver function. Associations between POPs and the biomarkers were then analysed using linear regression. Associations between POPs and incident liver disease (n = 36) were analysed by Cox regression. Organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and several perfluorinated alkyl substances exhibited statistically significant positive associations with several biomarkers of liver injury (betacoefficient per SD 0.04-0.14, p < 0.05). These associations were stronger in subgroups of individuals with obesity or non-alcoholic fatty liver disease. OCPs, PCBs and perfluoro-octanoic acid also had significant positive associations with dAAR, which can be used to predict risk of incident severe liver outcomes (beta coefficient per SD 0.05-0.08, p < 0.05). OCPs and PCBs were also significantly and positively associated with incident liver disease (hazard ratio per SD 1.82 95% CI 1.21-2.73, p < 0.01 and hazard ratio per SD 1.69, 95% CI 1.07-2.68, p < 0.05 respectively). Several POPs show positive associations with markers of liver injury and incident liver disease, suggesting that environmental toxins are important risk factors for chronic liver disease.

Role of EpCAM+ CD133+ extracellular vesicles in steatosis to steatohepatitis transition in NAFLD.

Extracellular vesicles (EVs) have emerged as a potential source of circulating biomarkers in liver disease. We evaluated circulating AV+ EpCAM+ CD133+ EVs as a potential biomarker of the transition from simple steatosis to steatohepatitis. EpCAM and CD133 liver proteins and EpCAM+ CD133+ EVs levels were analysed in 31 C57BL/6J mice fed with a chow or high fat, high cholesterol and carbohydrates diet (HFHCC) for 52 weeks. The hepatic origin of MVs was addressed using AlbCrexmT/mG mice fed a Western (WD) or Dual diet for 23 weeks. Besides, we assessed plasma MVs in 130 biopsy-proven NAFLD patients. Hepatic expression of EpCAM and CD133 and EpCAM+ CD133+ EVs increased during disease progression in HFHCC mice. GFP+ MVs were higher in AlbCrexmT/mG mice fed a WD (5.2% vs 12.1%) or a Dual diet (0.5% vs 7.3%). Most GFP+ MVs were also positive for EpCAM and CD133 (98.3% and 92.9% respectively), suggesting their hepatic origin. In 71 biopsy-proven NAFLD patients, EpCAM+ CD133+ EVs were significantly higher in those with steatohepatitis compare to those with simple steatosis (286.4 ± 61.9 vs 758.4 ± 82.3; p < 0.001). Patients with ballooning 367 ± 40.6 vs 532.0 ± 45.1; p = 0.01 and lobular inflammation (321.1 ± 74.1 vs 721.4 ± 80.1; p = 0.001), showed higher levels of these EVs. These findings were replicated in an independent cohort. Circulating levels of EpCAM+ CD133+ MVs in clinical and experimental NAFLD were increased in the presence of steatohepatitis, showing high potential as a non-invasive biomarker for the evaluation and management of these patients.

Extracellular Vesicles as Markers of Liver Function: Optimized Workflow for Biomarker Identification in Liver Disease.

Liver diseases represent a significant global health burden, necessitating the development of reliable biomarkers for early detection, prognosis, and therapeutic monitoring. Extracellular vesicles (EVs) have emerged as promising candidates for liver disease biomarkers due to their unique cargo composition, stability, and accessibility in various biological fluids. In this study, we present an optimized workflow for the identification of EVs-based biomarkers in liver disease, encompassing EVs isolation, characterization, cargo analysis, and biomarker validation. Here we show that the levels of microRNAs miR-10a, miR-21, miR-142-3p, miR-150, and miR-223 were different among EVs isolated from patients with nonalcoholic fatty liver disease and autoimmune hepatitis. In addition, IL2, IL8, and interferon-gamma were found to be increased in EVs isolated from patients with cholangiocarcinoma compared with healthy controls. By implementing this optimized workflow, researchers and clinicians can improve the identification and utilization of EVs-based biomarkers, ultimately enhancing liver disease diagnosis, prognosis, and personalized treatment strategies.

Liver Fibrosis, Fat, and Iron Evaluation with MRI and Fibrosis and Fat Evaluation with US: A Practical Guide for Radiologists.

Quantitative imaging biomarkers of liver disease measured by using MRI and US are emerging as important clinical tools in the management of patients with chronic liver disease (CLD). Because of their high accuracy and noninvasive nature, in many cases, these techniques have replaced liver biopsy for the diagnosis, quantitative staging, and treatment monitoring of patients with CLD. The most commonly evaluated imaging biomarkers are surrogates for liver fibrosis, fat, and iron. MR elastography is now routinely performed to evaluate for liver fibrosis and typically combined with MRI-based liver fat and iron quantification to exclude or grade hepatic steatosis and iron overload, respectively. US elastography is also widely performed to evaluate for liver fibrosis and has the advantage of lower equipment cost and greater availability compared with those of MRI. Emerging US fat quantification methods can be performed along with US elastography. The author group, consisting of members of the Society of Abdominal Radiology (SAR) Liver Fibrosis Disease-Focused Panel (DFP), the SAR Hepatic Iron Overload DFP, and the European Society of Radiology, review the basics of liver fibrosis, fat, and iron quantification with MRI and liver fibrosis and fat quantification with US. The authors cover technical requirements, typical case display, quality control and proper measurement technique and case interpretation guidelines, pitfalls, and confounding factors. The authors aim to provide a practical guide for radiologists interpreting these examinations. © RSNA, 2023 See the invited commentary by Ronot in this issue. Quiz questions for this article are available in the supplemental material.

Prevalence and metabolic determinants of abnormal alanine aminotransferase: A cross-sectional study of Iranian adults, 2018-2022.

Alanine aminotransferase (ALT) is an enzyme whose activity became the principal biomarker for liver disease. In the current study, we aimed to determine the prevalence of abnormal ALT, as a surrogate of nonalcoholic fatty liver disease (NAFLD) and its associated determinants using different criteria among Tehranian subjects between 2018 and 2022. This is a cross-sectional study on 5676 Tehranian individuals aged 20-70 years. The weighted prevalence of abnormal ALT was calculated using both the National Health and Nutrition Examination Survey in the United States (US-NHANCE; ALT ≥30 U/L for females and ≥40 U/L for males) and the American College of Gastroenterology (ACG) guideline (ALT >25 U/L for females, and >33 U/L for males) thresholds. Moreover, uni/multivariable logistic regression analysis was performed to find the determinants of abnormal ALT. The weighted prevalence of abnormal ALT was 12.8% (7.6% females and 18% males) and 22.5% (17.7% females and 27.3% males) based on US-NHANCE and ACG criteria, respectively. Our results showed every decade increase in age decreased the risk of abnormal ALT by 32%. We also found that generally male gender, being overweight/obese, central adiposity, TG ≥6.9 mmol/L, non-HDL-C ≥3.37 mmol/L, lipid-lowering medications, pre-diabetes/T2DM were associated with abnormal ALT using different cutoff points. Moreover, among men resting tachycardia (≥90 beats per min), hypertension, and females past-smoker were also found as other determinants of abnormal ALT. High prevalence of abnormal ALT among non-elderly Iranian adults, especially among men, necessitates immediate multifaceted strategies by policymakers to prevent potential complications caused by NAFLD.

The Fatty Liver, Cirrhosis, and Liver Cancer Study (TENDENCY): Protocol for a Multicenter Case-Control Study.

Hepatocellular cancer (HCC) is associated with high mortality, and early diagnosis leads to better survival. Patients with cirrhosis, especially due to nonalcoholic fatty liver disease and viral hepatitis, are at higher risk of developing HCC and form the main screening group. The current screening methods for HCC (6-monthly screening with serum alpha fetoprotein and ultrasound liver) have low sensitivity; hence, there is a need for better screening markers for HCC. Our study, TENDENCY, aims to validate the novel screening markers (methylated septin 9, urinary volatile organic compounds, and urinary peptides) for HCC diagnosis and study these noninvasive biomarkers in liver disease. This is a multicenter, nested case-control study, which involves comparing the plasma levels of methylated septin 9 between confirmed HCC cases and patients with cirrhosis (control group). It also includes the comparison of urine samples for the detection of HCC-specific volatile organic compounds and peptides. Based on the findings of a pilot study carried out at University Hospital Coventry & Warwickshire, we estimated our sample size to be 308 (n=88, 29% patients with HCC; n=220, 71% patients with cirrhosis). Urine and plasma samples will be collected from all participants and will be frozen at -80 °C until the end of recruitment. Gas chromatography-mass spectrometry will be used for urinary volatile organic compounds detection, and capillary electrophoresis-mass spectrometry will be used for urinary peptide identification. Real-time polymerase chain reaction will be used for the qualitative detection of plasma methylated septin 9. The study will be monitored by the Research and Development department at University Hospital Coventry & Warwickshire. The recruitment stage was completed in March 2023. The TENDENCY study is currently in the analysis stage, which is expected to finish by November 2023. There is lack of effective screening tests for hepatocellular cancer despite higher mortality rates. The application of more sensitive plasma and urinary biomarkers for hepatocellular cancer screening in clinical practice will allow us to detect the disease at earlier stages and hence, overall, improve HCC outcomes. DERR1-10.2196/44264.

Symposium 10 - Biomarkers of liver diseases.

Symposium 10 - Biomarkers of liver diseases.

175 Years of Bilirubin Testing: Ready for Point-of-Care?

Bilirubin was first detected in blood in 1847 and since then has become one of the most widely used biomarkers for liver disease. Clinical routine bilirubin testing is performed at the hospital laboratory, and the gold standard colorimetric test is prone to interferences. The absence of a bedside test for bilirubin delays critical clinical decisions for patients with liver disease. This clinical care gap has motivated the development of a new generation of bioengineered point-of-care bilirubin assays. In this Perspective, recently developed bilirubin assays are critically discussed, and their translational potential evaluated.

Liver Assessment in Patients with Ataxia-Telangiectasia: Transient Elastography Detects Early Stages of Steatosis and Fibrosis.

Ataxia-telangiectasia (A-T) is a rare autosomal-recessive multisystem disorder characterized by pronounced cerebellar ataxia, telangiectasia, cancer predisposition, and altered body composition. Liver diseases with steatosis, fibrosis, and hepatocellular carcinoma are frequent findings in older patients but sensitive noninvasive diagnostic tools are lacking. To determine the sensitivity of transient elastography (TE) as a screening tool for early hepatic tissue changes and serum biomarkers for liver disease. Thirty-one A-T patients aged 2 to 25 years were examined prospectively from 2016-2018 by TE. In addition, we evaluated the diagnostic performance of liver biomarkers for steatosis and necroinflammatory activity (SteatoTest and ActiTest, Biopredictive, Paris) compared to TE. For calculation and comparison, patients were divided into two groups (<12, >12 years of age). TE revealed steatosis in 2/21 (10%) younger patients compared to 9/10 (90%) older patients. Fibrosis was present in 3/10 (30%) older patients as assessed by TE. We found a significant correlation of steatosis with SteatoTest, alpha-fetoprotein (AFP), HbA1c, and triglycerides. Liver stiffness correlated significantly with SteatoTest, ActiTest, HbA1c, and triglycerides. Liver disease is a common finding in older A-T patients. TE is an objective measure to detect early stages of steatosis and fibrosis. SteatoTest and ActiTest are a good diagnostic assessment for steatosis and necroinflammatory activity in patients with A-T and confirmed the TE results.

Ppb‐Level ethanol gas sensor of porous anodic aluminum oxide at room temperature

AbstractExcessive ethanol in breath can be an indicator of alcoholism and a biomarker of liver disease. Herein, we present a novel porous aluminum anodic oxide (AAO)‐based chemi‐capacitive sensor that can detect ppb‐levels of ethanol gas at room temperature. The oxalic acid‐based porous AAO is an amorphous material contaminated with Al(OH)3 and C2O42− ions (anion‐contamination), which react with adsorbed ethanol gas. The optimal resonance frequency of ethanol was determined to be 500 Hz, and the response to 200 ppm ethanol at this frequency was 1.56%. Especially, the limit of detection of ppb‐level (16.49 ppb) was obtained. The detection range, reliability, and selectivity of the sensor, as well as its surface properties were comprehensively investigated. The proposed sensor is promising for the detection of liver disease as well as for commercial breath ethanol analyzers.

Krüppel-like factor 15 in liver diseases: Insights into metabolic reprogramming.

Liver diseases, characterized by metabolic disorder, have become a global public health problem with high morbidity and mortality. Krüppel-like factor 15 (KLF15) is a zinc-finger transcription factor mainly enriched in liver. Increasing evidence suggests that hepatic KLF15 is activated rapidly during fasting, and contributes to the regulation of gluconeogenesis, lipid, amino acid catabolism, bile acids, endobiotic and xenobiotic metabolism. This review summarizes the latest advances of KLF15 in metabolic reprogramming, and explore the function of KLF15 in acute liver injury, hepatitis B virus, and autoimmune hepatitis. which aims to evaluate the potential of KLF15 as a therapeutic target and prognostic biomarker for liver diseases.

Lifestyle Intervention in NAFLD: Long-Term Diabetes Incidence in Subjects Treated by Web- and Group-Based Programs.

Behavioral programs are needed for prevention and treatment of NAFLD and the effectiveness of a web-based intervention (WBI) is similar to a standard group-based intervention (GBI) on liver disease biomarkers. We aimed to test the long-term effectiveness of both programs on diabetes incidence, a common outcome in NAFLD progression. 546 NAFLD individuals (212 WBI, 334 GBI) were followed up to 60 months with regular 6- to 12-month hospital visits. The two cohorts differed in several socio-demographic and clinical data. In the course of the years, the average BMI similarly decreased in both cohorts, by 5% or more in 24.4% and by 10% or more in 16.5% of cases available at follow-up. After excluding 183 cases with diabetes at entry, diabetes was newly diagnosed in 48 cases during follow-up (31 (16.6% of cases without diabetes at entry) in the GBI cohort vs. 17 (9.7%) in WBI; p = 0.073). Time to diabetes was similar in the two cohorts (mean, 31 ± 18 months since enrollment). At multivariable regression analysis, incident diabetes was significantly associated with prediabetes (odds ratio (OR) 4.40; 95% confidence interval (CI) 1.97-9.81; p < 0.001), percent weight change (OR 0.57; 95% CI 0.41-0.79; p < 0.001) and higher education (OR 0.49; 95% CI 0.27-0.86; p = 0.014), with no effect of other baseline socio-demographic, behavioral and clinical data, and of the type of intervention. The importance of weight change on incident diabetes were confirmed in a sensitivity analysis limited to individuals who completed the follow-up. In individuals with NAFLD, WBI is as effective as GBI on the pending long-term risk of diabetes, via similar results on weight change.

Hepatocyte-derived DPP4 regulates portal GLP-1 bioactivity, glucose production, and its absence alters liver disease progression.

Elevated circulating dipeptidyl-peptidase 4 is a biomarker for liver disease, but its involvement in gluconeogenesis and in metabolic-associated fatty liver disease (MAFLD) progression remains unclear. Here we identified that DPP4 in hepatocytes but not Tie2+ endothelial cells regulates the local bioactivity of incretin hormones and gluconeogenesis. However, the complete absence of DPP4 (Dpp4-/-) in aged mice with metabolic syndrome accelerates liver fibrosis without altering dyslipidemia and steatosis. Analysis of transcripts from the livers of whole body Dpp4-/- displayed enrichment for inflammasome, p53, and senescence programs compared to littermate controls. High-fat high-cholesterol (HFHC)-feeding decreased Dpp4 expression in F4/80+ cells, with only minor changes in immune signaling. Moreover, in a lean mouse model of severe non-alcoholic fatty liver disease (NAFLD), phosphatidylethanolamine N-methyltransferase (Pemt -/-) mice fed with HFHC diet, we observed a 4-fold increase in circulating DPP4, disassociating its release from obesity. Lastly, we evaluated DPP4 levels in patients with hepatitis C infection with dysglycemia (HOMA-IR > 2) who underwent direct antiviral treatment (with or without ribavirin). DPP4 protein levels decreased with viral clearance, and DPP4 activity levels were reduced at longer-term follow-up in ribavirin-treated patients, although metabolic factors did not improve. These data suggest elevations in DPP4 during HCV infection are not primarily regulated by metabolic disturbances.

An ultrasensitive isoprene gas sensor based on the In2O3/MoS2 nanocomposite prepared by hydrothermal synthesis.

Isoprene is one of the specific biomarkers of liver disease in human exhaled gas, which should be detected with a high response at an order of ppb in actual application. In this paper, the heterojunction between n-type In2O3 and MoS2 was proposed to improve the isoprene sensing properties. Both In2O3 and MoS2 were prepared by a hydrothermal method, and nanostructured In2O3 flowers and solid micro irregular MoS2 particles were mixed into the In2O3/MoS2 composite with a mol ratio of 6 : 4. The composite was characterized by EDS and XRD to confirm the element types and crystal types. The isoprene sensor was prepared by dipping the composite suspension on a ceramic substrate integrated with a sensing electrode and heating unit. The testing results of the sensor showed the highest response value of 1.8 to 100 ppb isoprene at 200 °C. Besides, the low detecting limit (less than 5 ppb isoprene) and excellent selectivity are also revealed, showing that the composite can be a good candidate sensing material for isoprene for application in breath analysis.

Extracellular Vesicles as Biomarkers in Liver Disease.

Extracellular vesicles (EVs) are membrane-derived vesicles released by a variety of cell types, including hepatocytes, hepatic stellate cells, and immune cells in normal and pathological conditions. Depending on their biogenesis, there is a complex repertoire of EVs that differ in size and origin. EVs can carry lipids, proteins, coding and non-coding RNAs, and mitochondrial DNA causing alterations to the recipient cells, functioning as intercellular mediators of cell-cell communication (auto-, para-, juxta-, or even endocrine). Nevertheless, many questions remain unanswered in relation to the function of EVs under physiological and pathological conditions. The development and optimization of methods for EV isolation are crucial for characterizing their biological functions, as well as their potential as a treatment option in the clinic. In this manuscript, we will comprehensively review the results from different studies that investigated the role of hepatic EVs during liver diseases, including non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcoholic liver disease, fibrosis, and hepatocellular carcinoma. In general, the identification of patients with early-stage liver disease leads to better therapeutic interventions and optimal management. Although more light needs to be shed on the mechanisms of EVs, their use for early diagnosis, follow-up, and prognosis has come into the focus of research as a high-potential source of 'liquid biopsies', since they can be found in almost all biological fluids. The use of EVs as new targets or nanovectors in drug delivery systems for liver disease therapy is also summarized.

Effect of semaglutide on fatty liver disease biomarkers in patients with diabetes and obesity

AimThis work aims to assess the effect of weekly subcutaneous semaglutide on biomarkers of metabolic-associated fatty liver disease (MAFLD), namely the hepatic steatosis index (HSI) and the fibrosis-4 (FIB-4) index, at 24 weeks in outpatients attended to in internal medicine departments. MethodsThis study analyzed patients in an ongoing, multicenter, prospective, pre-post, uncontrolled cohort registry that enrolls unique, consecutive patients with type 2 diabetes treated with weekly subcutaneous semaglutide. Steatosis/fibrosis were determined by HSI (<30 ruled out, >36 steatosis) and FIB-4 (<1.3 ruled out, >2.67 fibrosis), respectively. ResultsThe sample included 213 patients (46.9% women) with a median age of 64 (19) years. The median baseline body mass index and weight were 36.1 (8.4) kg/m2 and 98 (26.9) kg, respectively. A total of 99.9% had HSI values indicating steatosis, with a mean HSI of 47.9 (8.2). Additionally, 10.8% had fibrosis (FIB-4 > 2.67) and 42.72% had values in intermediate ranges (FIB-4 1.3-2.67). At 24 weeks, there was a significant reduction in HSI (-2.36 (95%CI 1.83-2.9) p < 0.00001) and FIB-4 (-0.075 (95%CI 0.015-0.14) p < 0.016), mainly related to declines in body weight, triglyceride levels, insulin resistance (estimated by the triglyceride-glucose index), and liver enzymes. ConclusionThese results show that weekly subcutaneous semaglutide had a beneficial effect on liver steatosis that went beyond glucose control. Its effects were mainly related to weight loss, a decline in biomarkers, and improvements in insulin sensitivity. For many patients, early detection is essential for improving MAFLD outcomes and may allow for selecting the most efficient treatment options.

Expeditious fluorimetric detection of bilirubin by simple imidazole derived luminophore and it's pragmatic applicability in spiked biological fluids

Bilirubin is an indispensable biomarker for liver diseases. Utilizing organic molecules as sensor platform for effective detection of bilirubin are little. In addition, the reported fluorophores required longer incubation time for detection. Hence, herein we have attempted to design an imidazole derivative 4-(3H-imidazo[4,5-b]pyridin-2-yl)-N,N-diphenylaniline (IMI) from triphenylamine and pyridine units which could detect bilirubin swiftly without any incubation period. IMI manifested an instant quenching of emission in presence of bilirubin with limit of detection (LOD) 11.74 × 10−6 mol L−1. The mechanistic aspect of detection involves coexistence of both static and dynamic quenching which was suitably justified. Finally, the pragmatic application of IMI was performed in bio-fluids.

Setting up of a machine learning algorithm for the identification of severe liver fibrosis profile in the general US population cohort

BackgroundThe progress of digital transformation in clinical practice opens the door to transforming the current clinical line for liver disease diagnosis from a late-stage diagnosis approach to an early-stage based one. Early diagnosis of liver fibrosis can prevent the progression of the disease and decrease liver-related morbidity and mortality. We developed here a machine learning (ML) algorithm containing standard parameters that can identify liver fibrosis in the general US population. Materials and methodsStarting from a public database (National Health and Nutrition Examination Survey, NHANES), representative of the American population with 7265 eligible subjects (control population n = 6828, with Fibroscan values E < 9.7 KPa; target population n = 437 with Fibroscan values E ≥ 9.7 KPa), we set up an SVM algorithm able to discriminate for individuals with liver fibrosis among the general US population. The algorithm set up involved the removal of missing data and a sampling optimization step to managing the data imbalance (only ∼ 5 % of the dataset is the target population). ResultsFor the feature selection, we performed an unbiased analysis, starting from 33 clinical, anthropometric, and biochemical parameters regardless of their previous application as biomarkers of liver diseases. Through PCA analysis, we identified the 26 more significant features and then used them to set up a sampling method on an SVM algorithm. The best sampling technique to manage the data imbalance was found to be oversampling through the SMOTE-NC. For final model validation, we utilized a subset of 300 individuals (150 with liver fibrosis and 150 controls), subtracted from the main dataset prior to sampling. Performances were evaluated on multiple independent runs. ConclusionsWe provide proof of concept of an ML clinical decision support tool for liver fibrosis diagnosis in the general US population. Though the presented ML model represents at this stage only a prototype, in the future, it might be implemented and potentially applied to program broad screenings for liver fibrosis.

Current and Emerging Molecular Markers of Liver Diseases: A Pathogenic Perspective.

In the past decade, with the rapid development of molecular medicine and the application of more sophisticated methods for disease diagnosis and treatment, a number of molecular markers have become available for liver diseases. Pathogenesis-related markers are likely to be effectively discovered and rigorously validated, due to the unique biological links to diseases. The present study reviews the predominant clinical and research articles in the previous decade to provide a pathogenic perspective of current and emerging biomarkers for liver diseases, including hepatocellular neoplasms (e.g. hepatocellular carcinoma), non-neoplastic hepatocellular diseases, intrahepatic biliary diseases, and other liver diseases. Although it remains challenging to cover all markers for the diagnosis and prognosis of liver diseases, current and emerging molecular markers in clinical practice and under investigation are reviewed in a wide spectrum of liver diseases, in order to help clinicians and researchers identify liver disease markers for reference.

Identification and chemical profiling of anti-alcoholic liver disease biomarkers of ginseng Huang jiu using UPLC-Q-Orbitrap-HRMS and network pharmacology-based analyses

This study investigated the mechanism of characteristic non-volatile organic compounds (NVOCs) from ginseng Huang jiu (GH) in the treatment of alcoholic liver disease through UPLC-Q-Orbitrap-HRMS and network pharmacological analyses. Changes in NVOC contents in ginseng Huang jiu and ginseng-soaked wine fermented by different processing technologies were analyzed through liquid chromatography–mass spectrometry (LC-MS). A total of 96 ginsenosides were identified in ginseng Huang jiu throughout the fermentation process, which included 37 protopanaxadiol-type ginsenosides, 47 protopanaxatriol-type ginsenosides, and 4 oleanolic acid-type ginsenosides. Orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed that 20(R)-Rg2, Gypenoside XVII, 20(S)-Rf3, CK, Rg5, Rh2, and other rare ginsenosides in ginseng Huang jiu could be the potential index for determining ginseng Huang jiu. In addition, ginseng Huang jiu could improve alcoholic liver disease by regulating the GSTP1, HRAS, AKR1B1, GSTA1, Androgen receptor (AR), GSR, and LDHB genes through bioinformatics analysis. This study provides new insights into improving the industrial production of ginseng Huang jiu and treating alcoholic liver disease with medicinal and food products.