Alcoholic Liver Research Articles

Characterizing alcohol-related and metabolic dysfunction-associated steatotic liver disease cirrhosis via fibrotic pattern analysis

This study aimed to address the diagnostic challenges in distinguishing between alcohol-related liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD). We utilized whole-slide imaging technology to conduct a comprehensive digital analysis of liver specimens collected from patients undergoing transplantation. This study included 36 and 17 patients with ALD and MASLD cirrhosis, respectively, who underwent transplantation at our institution. Digital slides were analyzed for fibrosis patterns using FibroNest™. Patient background characteristics were comparable between ALD (n = 36) and MASLD (n = 17) groups, except for sex. The ALD group exhibited thicker collagen per strand, longer and more flexural fibrosis, and a more heterogeneous distribution than the MASLD group. In patients with ALD and concomitant metabolic dysfunction, fiber distribution became relatively uniform, resembling MASLD. Application of the phenotypic fibrosis composite score achieved 100% sensitivity and specificity for ALD/MASLD diagnosis. Digital pathological analysis of the fibrosis patterns showed morphological differences between ALD and MASLD. This approach holds promise for histological differentiation, providing valuable insights beyond the current definitions based solely on alcohol intake. This study emphasizes the potential of digital pathology in refining the diagnostic criteria for hepatic disorders.

Protective mechanisms of Hovenia dulcis Thunb extracts on acute alcoholism and liver injury

As a traditional Chinese medicine for anti-alcoholism, Hovenia dulcis Thunb (HDT) is widely used in the treatment of alcoholism and alcohol-related liver diseases. However, the scientific evidence of its mechanism has not been clearly established. In this study, a mouse model of acute alcoholism was established to explore the protective mechanisms of three kinds of HDT extracts on acute alcoholism and liver injury from the perspectives of behavioral indicators, serum and liver biochemical indicators, alcohol metabolic enzyme activity, intestinal flora, and liver metabolomics. The results showed that the extracts of HDT shortened the time of sobering up, significantly increased the activity of alcohol metabolic enzymes and antioxidant capacity, promoted ethanol metabolism, and had a certain preventive effect on alcoholic liver injury while preventing adverse reactions caused by alcohol. Notably, HDT water extract (HDTs) demonstrated superior anti-alcohol and liver protective properties compared to polysaccharide and polyphenol extracts of HDTs. It may be through the regulation of intestinal flora imbalance, specifically Muribaculaceae and Dubosiella to modulate biosynthetic pathways of phenylalanine, tyrosine, and tryptophan, ultimately mitigating oxidative stress caused by ethanol consumption. This suggests that HDTs may have potential in preventing acute alcoholism and liver injury.

Effects of four-week lasting aerobic treadmill training on hepatic injury biomarkers, oxidative stress parameters, metabolic enzymes activities and histological characteristics in liver tissue of hyperhomocysteinemic rats.

Disruptions in homocysteine (Hcy) metabolism may increase the liver's susceptibility to developing conditions such as alcoholic liver disease, viral hepatitis, hepatocellular carcinoma (HCC), and cirrhosis. The aim of this study was to examine effects of aerobic treadmill training on hepatic injury biomarkers in sera, oxidative stress parameters, the activity of metabolic enzymes, and histological characteristics in the liver tissue of rats with experimentally induced hyperhomocysteinemia. Male Wistar albino rats were divided into four groups (N = 10, per group): C-saline 0.2mL/day sc. 2×/day for 14days + saline 0.5mL ip.1×/day for 28days; H-homocysteine 0.45µmol/g b.w. 2×/day for 14days + saline 0.5mL ip.1×/day for 28days; CPA-saline 0.2mL/day sc. 2×/day for 14days + aerobic treadmill training for 28days; and HPA-homocysteine 0.45µmol/gb.w. 2×/day for 14days + aerobic treadmill training for 28days. The serum albumin concentration was decreased in both physically active (PA) groups compared to sedentary groups. Concentration of malondialdehyde in liver tissue homogenates was lower in both PA groups compared to the H group. The total lactate dehydrogenase and malate dehydrogenase activities were significantly elevated in the HPA group compared to the C and H groups. Activities of aminotransferases in sera samples, and activities of catalase and superoxide dismutase in liver tissue did not significantly differ between groups. No significant histological changes were found in liver tissue in groups. This study demonstrated that aerobic treadmill training can reduce lipid peroxidation in liver tissue under hyperhomocysteinemic conditions, providing a protective effect. However, hyperhomocysteinemia can alter energy metabolism during aerobic exercise, shifting it toward anaerobic pathways and leading to elevated lactate dehydrogenase activity in the liver. Given that conditions like hyperhomocysteinemia are associated with an increased risk of cardiovascular diseases and liver damage, understanding how exercise influences these dynamics could guide therapeutic approaches.

Lactiplantibacillus plantarum P101 Alleviated Alcohol-Induced Hepatic Lipid Accumulation in Mice via AMPK Signaling Pathway: Gut Microbiota and Metabolomics Analysis.

Mitigating steatosis is essential for delaying the progression of alcoholic liver disease. The effect and mechanism of Lactiplantibacillus plantarum P101 (LP.P101) on alleviating alcohol-induced hepatic lipid accumulation were investigated in our study. The mouse model was constructed by a short-term (10-day)-plus-binge ethanol feeding and gavaged with 108 CFU/mL of LP.P101 daily. Lipid droplet in the liver was significantly reduced by LP.101 intervention on AMPK activation. However, when AMPK was inhibited by dorsomorphin, the levels of related indicators (ALT, TG, etc.) and the expression levels of AMPK and relevant genes in the liver converged to that of the alcohol-fed group. Compared with the alcohol-fed group, LP.P101 reduced the relative abundance of Firmicutes and increased that of Bacteroidetes. Parabacteroides merdae was negatively correlated with lipid accumulation, and unclassified Negativibacillus was negatively associated with AMPK activation. Importantly, LP.P101 modified the compositions of the serum metabolites. The potential biomarker stercobilinogen was positively correlated with AMPK activation and negatively associated with lipid accumulation. This work confirmed that LP.P101 attenuated alcohol-induced hepatic lipid accumulation in mice through AMPK activation, and the alterations in gut microbiota and metabolites may play a significant role on AMPK activation.

Role of Ferroptosis in ALD: Focusing on Hepcidin and Besides Hepcidin.

Ascending incidence and poor outcomes make Alcoholic Liver Disease (ALD) a considerable public health concern. This review concluded the iron metabolism under physiology conditions and alcohol disturbance (leading to ferroptosis in ALD) and summarized the novel treatment, diagnosis, and prognosis of ferroptosis for ALD. ALD is characterized by alcohol-induced chronic metabolism disorder, peroxidation damage, and dysfunction of the anti-oxidant system. Current animal experiments and clinical studies identified ferroptosis as a new form of regulated cell death involved in ALD. One strong evidence is that the key iron regulatory hormone, hepcidin, is downgraded in ALD through NF-κB/IL-6/STAT3, BMP/SMAD, and Jak/STAT3 pathways, which would impair iron hemostasis and induce ferroptosis in ALD. Also, imbalance metabolism and other pathological responses in ALD induce and regulate ferroptosis, which proves ferroptosis participates in the pathophysiology of ALD via oxidative stress, steatosis, and fibrosis. Inhibition of ferroptosis via regulating hepcidin expression and metabolism impairment may provide new therapies for ALD.

Puerarin: a hepatoprotective drug from bench to bedside.

Pueraria is a time-honored food and medicinal plant, which is widely used in China. Puerarin, the main component extracted from pueraria, has a variety of pharmacological characteristics. In recent years, puerarin has received increasing attention for its significant hepatoprotective effects, such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma. This paper explores the pharmacological effects of puerarin on various liver diseases through multiple mechanisms, including inflammation factors, oxidative stress, lipid metabolism, apoptosis, and autophagy. Due to its restricted solubility, pharmacokinetic studies revealed that puerarin has a low bioavailability. However, combining puerarin with novel drug delivery systems can improve its bioavailability. Meanwhile, puerarin has very low toxicity and high safety, providing a solid foundation for its further. In addition, this paper discusses puerarin's clinical trials, highlighting its unique advantages. Given its excellent pharmacological effects, puerarin is expected to be a potential drug for the treatment of various liver diseases.

Hepatoprotective Effect of Antrodia camphorata Mycelium Powder on Alcohol-Induced Liver Damage

Background/Objectives: Antrodia camphorata, also known as “Niuchangchih” in Taiwan, is a unique medicinal mushroom native to Taiwan. It is used in traditional medicine to treat various health conditions. In this study, we investigated the efficacy of A. camphorata mycelia on alcohol-induced liver damage, both in vitro and in vivo, in a Good Laboratory Practice (GLP) facility. Methods: The experimental groups consisted of a normal control group (G1), a negative control group (G2), an A. camphorata mycelium powder 50 mg/kg/day administration group (G3), a 100 mg/kg/day administration group (G4), a 200 mg/kg/day administration group (G5), and a positive control silymarin 200 mg/kg/day administration group (G6), with 10 Sprague Dawley rats assigned to each treatment group. Results: We found that treatment with A. camphorata mycelium powder significantly reduced alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, cholesterol, adiponectin, triglyceride, and malondialdehyde concentrations. Histopathological analysis also revealed that the inflammation score significantly decreased in the A. camphorata-treated groups. Conclusion: Based on these results, we conclude that repeated oral administration of A. camphorata mycelium powder is effective in improving alcoholic liver disease.

The association of systemic inflammatory biomarkers with metabolic dysfunction-associated steatotic liver disease and arterial hypertension

Objective — to explore the relationship between metabolic dysfunction‑associated steatotic liver disease (MASLD) on the background of arterial hypertension (AH) and blood inflammatory markers including C‑reactive protein (CRP), Interleukin‑6 (IL‑6), IL‑4, haptoglobin and pentraxin‑3 (PTX‑3). Materials and methods. We examined 102 patients with MASLD. They were divided into 3 groups: group A included 52 patients with isolated MASLD, group B — 23 patients with MASLD and AH stage I, and group C — 27 patients with MASLD and AH stage II. The control group (group D) comprised 20 apparently healthy people. Patients with viral hepatitis, liver cirrhosis, alcoholic liver disease, and AH stage III were excluded. Systemic inflammatory biomarkers analyses were performed using electrochemiluminescence, immunoenzymatic, and immunoturbidimetry techniques. Results. The systemic inflammatory biomarkers analyses revealed significantly higher levels of CRP (p=0.001), IL‑6 (p=0.01), haptoglobin (p<0.05) and PTX‑3 (p<0.01) and decreased levels of IL‑4 (p<0.05) in group B and group C in comparison with the group A and control group (p1 <0.01, p2=0.01). Also, there was a significant increase of CRP (p=0.01), IL‑6 (p=0.01), and PTX‑3 levels (p<0.05) in group B compared with group C. However, the relationship between the IL‑4 (p>0.05) and haptoglobin (p>0.05) levels and the progression of the AH stages have not been confirmed in our study. Conclusions. Our findings indicate the direct relationship between the systemic inflammatory biomarkers’ involvement in developing liver tissue inflammation and the further progression of MASLD. The obtained data indicate the relationship of AH and its stages with the development of chronic systemic inflammatory response in patients with MASLD and AH comorbid course.

Alcoholic Hepatitis: A Paradigm shift of Prevention and Treatment Analyzed at Cellular level by Histo/Pathological Micrometric Assessment.

Objective: To evaluate role of Vitamin C and Naproxen in Alcohol-induced liver toxicity by micrometric technique (hepatocyte count, size and nuclear diameter) in albino rats.Methodology: This experimental interventional study was conducted at the sheikh Zayed medical college and hospital Rahim yar khan from December 2022 to March 2023. 60 albino rats with equal gender distribution were selected based on the random probability sampling technique and placed in three groups of 20, again with an equal gender distribution (1:1). Group A (positive control) was given purified Ethanol for 10 days., Group B was given Vitamin C and NaproxenProphylaxis for 7 days and later intoxicated with Ethanol for 10 days and Group C was simultaneously Administered Vitamin C, Naproxen, and Ethanol for 10 days. The hepatocyte count, size and nuclear diameter of all the groups were recorded by micrometric technique using ocular and stage micrometric scales. Data analysis was conducted using SPSS 24.0 and P-Value of ≤0.05 considered Statistically Significant.Results: Group A animals experienced decreased number of hepatocyte count, increase in size of cell and decrease in nucleus size; Group B showed similar picture as group “A” but less in intensity and Group C showed nearly normal hepatic architecture with hepatocyte count, size and nuclear size close to normal ranges.Conclusion: The anti-oxidative and anti-inflammatory effects of Vitamin C and Naproxen demonstrated significant hepatoprotective effects on liver histologic architecture, providing safety from alcohol-induced liver injury. Keywords: Naproxen, Prophylaxis, liver toxicity, alcoholic liver disease, vitamin C.

Liver Dysfunction and Systemic Inflammation Drive Organ Failures in Acute Decompensation of Cirrhosis: A Multicentric Study.

Hospitalized patients with acute decompensation (AD) of cirrhosis are at risk of progressing to acute-on-chronic liver failure (ACLF), significantly increasing their mortality. The aim of this study was to identify key predictors and patient trajectories predisposing to ACLF. In this multicenter, prospective study spanning 2 years, clinical, biochemical, and 90-day survival data were collected from 625 patients with AD (European Association for the Study of the Liver criteria) across North, South, and East India. We divided the cohort into a Derivation cohort (DC: 318 patients) and a Validation cohort (VC: 307 patients). Predictive models for pre-ACLF were derived, validated, and compared with established scores such as model for end-stage liver disease (MELD) 3.0 and chronic liver failure Consortium acute decompensation. Of 625 patients (mean age 49 years, 83% male, 77.5% with alcohol-related liver disease), 32.2% progressed to ACLF. Patients progressing to ACLF showed significantly higher bilirubin (10.9 vs 8.1 mg/dL), leukocyte counts (9,400 vs 8,000 per mm 3 ), international normalized ratio (1.9 vs 1.8), and MELD 3.0 (28 vs 25) but lower sodium (131 vs 134 mEq/L) and survival (62% vs 86%) compared with those without progression ( P < 0.05) in the DC. Consistent results were noted with alcohol-associated hepatitis, infection and hepatic encephalopathy as additional risk factors in VC. Liver failure at presentation (odds ratio: 2.4 [in DC], 6.9 [in VC]) and the 7-day trajectories of bilirubin, international normalized ratio, and MELD 3.0 significantly predicted ACLF progression ( P < 0.001). A new pre-ACLF model showed superior predictive capability (area under the curve of 0.71 in DC and 0.82 in VC) compared with MELD 3.0 and chronic liver failure Consortium acute decompensation scores ( P < 0.05). Approximately one-third of AD patients in this Indian cohort rapidly progressed to ACLF, resulting in high mortality. Early identification of patients at risk can guide targeted interventions to prevent ACLF.

Qiwei Jinggan Ling regulates oxidative stress and lipid metabolism in alcoholic liver disease by activating AMPK

BackgroundAlcoholic liver disease (ALD) is a severe public health concern worldwide and there is still a lack of effective treatments. Qiwei Jinggan Ling (QJL) has protective effects against various liver injuries, but its pharmacological action on ALD has received little attention. PurposeTo investigate the effect and mechanism of QJL on ALD in vivo and in vitro. MethodsIn vivo, an ALD mouse model was established by alcohol combined with a high-fat diet (HFD) and treated with QJL. Biochemical indicators, HE staining, and Oil Red O staining were employed to assess hepatic oxidative stress, steatosis, and alcohol metabolism. RNA sequencing analysis was performed, and the results were verified by qRT-PCR and Western blot to elucidate the hepatoprotective mechanism of QJL. In vitro, HepG2 cells were co-stimulated with NaOA (sodium oleate) and EtOH (ethanol), followed by intervention with Compound C (CC, AMPK inhibitor) and QJL-containing serum. Oil Red O, BODIPY (boron-dipyrromethene), and ROS (reactive oxygen species) staining were applied to validate the efficacy and mechanism of QJL-containing serum. The expression of AMP-activated protein kinase (AMPK) pathway-related factors was analyzed through qRT-PCR and Western blot for additional corroboration. Moreover, the key pharmacodynamic components of QJL were identified by UPLC-MS/MS and molecular docking. ResultsIn vivo, QJL ameliorated liver structural disorders, steatosis, oxidative stress, and impaired alcohol metabolism, as indicated by biochemical indicators and histopathological assays. RNA sequencing analysis revealed that QJL reversed the expression of genes related to alcohol metabolism, fatty acid metabolism, and cholesterol metabolism. The results of qRT-PCR and Western blot were in line with those of RNA sequencing. Furthermore, it was discovered that QJL significantly upregulated the expression of p-AMPK and downregulated the expression of sterol regulatory element binding transcription factor 1 (SREBP-1c). In vitro, biochemical indicators and staining assays demonstrated that QJL-containing serum inhibited lipid accumulation and oxidative stress. The qRT-PCR and Western blot analysis revealed that QJL-containing serum markedly enhanced the expression of p-AMPK and carnitine palmitoyltransferase 1a (Cpt1a), while suppressing the expression of SREBP-1c, fatty acid synthase (Fasn), and acetyl-coenzyme A carboxylase 1 (ACC-1). However, CC inhibited the above pharmacological activities of QJL-containing serum. Additionally, (2S)-Liquiritigenin, Glycyrrhetinate, Isovitexin, Taxifolin, and Yohimbine were proved to be the key active components of QJL. ConclusionQJL had the potential to be a therapeutic drug for ALD by activating the AMPK pathway, thereby regulating lipid metabolism and inhibiting oxidative stress.

Deciphering the impact and mechanism of total flavonoids from Cortex Juglandis Mandshuricae on alcoholic fatty liver employing LC-MS/MS, network pharmacology analysis and in vitro validation

The Cortex Juglandis Mandshuricae (CJM) has the efficacy of penetrating the liver meridian, removing heat and dampness, and alleviating the liver, which corresponds to the pathogenesis of alcoholic fatty liver disease (AFLD) with damp heat accumulation. Modern research has shown that total flavonoids from Cortex Juglandis Mandshuricae (TFC) have hepatoprotective, antioxidant and antitumour pharmacological effects. However, there is no any investigation on the mechanism of TFC improving AFLD. In this work, a valid strategy combining UPLC-Q-Exactive Orbitrap-MS, network pharmacology and in vitro cellular experimental validation is proposed to predict the targets and pathways of total flavonoids from Cortex Juglandis Mandshuricae (TFC) to ameliorate AFLD and to explore its mechanism of action. As a result, 26 flavonoids and 182 targets linked to TFC and AFLD were identified. These compounds realize their critical targets via various signaling pathways and perform multiple biological functions on the basis of the constructed compound-disease target networks. In vitro experiments demonstrated TFC had a protective impact on ethanol-treated L02 cells to a certain extent and could diminished lipid accretion. In addition, RT-qPCR and western blot results illustrated that TFC could regulate the expression of PPARα, CPT-1, SREBP-1c and FAS, and inhibit alcohol-induced lipid accumulation in L02 cells thereby alleviating AFLD. The present study further provides experimental justification for TFC to ameliorate AFLD in practical applications.

Hepatocellular carcinoma risk scores for non-viral liver disease: A systematic review and meta-analysis

BackgroundHepatocellular carcinoma (HCC) risk prediction models may provide a more personalised approach to surveillance for HCC among patients with cirrhosis. This systematic review aims to summarise the performance of HCC prediction models in patients with non-viral chronic liver disease. MethodThe study was prospectively registered with PROSPERO (ID: CRD42022370078) and reported in accordance with PRISMA guidelines. MEDLINE and EMBASE databases were searched using a validated search filter for prediction model studies. Two reviewers independently assessed studies for inclusion and risk of bias. Model performance (discrimination and calibration) were identified to assess the risk of HCC at specified time points. A random effects meta-analysis was done on a subset of studies that reported performance of the same model. Results7,854 studies were identified. After review, 14 studies with a total of 94,014 participants were included. 45% of patients had viral hepatitis, 27% alcohol related liver disease (ArLD) and 19% metabolic associated steatotic liver disease (MASLD). Follow-up ranged from 15.1 - 138 months. Only one model was developed using a competing risk approach. Age (7 models) and sex (6 models) were the most frequently included predictors. Model discrimination (AUROC or c-statistic) ranged from 0.61 - 0.947. Only the ‘aMAP’ score (age, male sex, albumin,bilirubin, and platelets) had sufficient external validation for quantitative analysis, with a pooled c-statistic of 0.81 (95% CI 0.80-0.83). Calibration was reported in only 9 of 14 studies. All studies were rated high risk of bias. ConclusionStudies describing risk prediction of HCC in non-viral chronic liver disease are poorly reported, have a high risk of bias and do not account for competing risk events. Patients with ArLD and MASLD are underrepresented in development and validation cohorts. These factors remain barriers to the clinical utility and uptake of HCC risk models in persons with the commonest liver diseases. Impact and implicationsThe recent EASL policy statement emphasises the potential of risk-based surveillance to reduce both HCC-related deaths and surveillance costs. This study addresses the gap in understanding the performance of current HCC risk models in patients with non-viral liver diseases, reflecting the epidemiological landscape of liver disease in Western countries.In our review of these models, we identified several key concerns regarding reporting standards and risk of bias and confirmed that patients with alcohol-related liver disease (ArLD) and metabolic-associated steatotic liver disease (MASLD) are underrepresented in model development and validation cohorts. Additionally, most models fail to account for the significant risk of competing events, leading to potential overestimation of true HCC risk.This study highlights these critical issues that may hinder the implementation of risk models in clinical practice and offers key recommendations for future model development studies.

Protective effects of phenylethanol glycosides from Cistanche tubulosa against ALD through modulating gut microbiota homeostasis

Ethnopharmacological relevanceCistanche tubulosa (Schenk) Wight, a Chinese herbal medicine (Rou Cong Rong) with Xinjiang characteristics, was recorded in many medical books in ancient China and often used as a tonic medicine. Supported by the traditional Chinese medicine theory of “homology of liver and kidney,” C. tubulosa (Schenk) Wight has many clinical applications in tonifying the kidney and protecting the liver. Modern pharmacological studies have also found that the protective effects of phenylethanol glycosides from C. tubulosa (Schenk) Wight (CPhGs) play an important role in ameliorating alcoholic liver injury. Aim of the studyWe aimed to investigate whether CPhGs can enhance the therapeutic outcome of alcoholic liver disease (ALD) by targeting the “gut–liver axis,” thus contributing to the knowledge of how Chinese herbs alleviate disease by influencing the gut microbiota. Materials and methodsAn ALD mouse model was established using the Lieber–DeCarli alcohol liquid diet, and the effects of CPhGs on the intestinal barrier and gut microbiota of ALD mice were investigated in a pseudo-sterile mouse model and fecal microbiota transplantation (FMT) mouse model. We fed female C57BL/6N mice with Lieber-DeCarli ethanol liquid diet, according to the NIAAA model. Animal experiment of long-term, ethanol diet intervention for 6W, and short-term for 11d. The FMT experiments were also performed. ResultsCPhGs significantly improved ALD manifestations. ALD mice demonstrated significant gut microbiota dysbiosis and significantly abnormal proliferation of Allobaculum compared with the control diet group in long-term NIAAA mouse model (L-Pair). In mice that received the long-term intervention, the improvement in gut barrier function in the CPhGs-treated group was accompanied by a significant decrease in the abundance of Allobaculum and a significant increase in the abundance of Akkermansia. Furthermore, compared with the mouse were gavaged fecal microbiota from the long-term NIAAA mouse donors (FMT-EtOH), the number of goblet cells, abundance of Akkermansia, and the intestinal short-chain fatty acid concentrations were significantly increased in the mouse were gavaged fecal microbiota from high (700 mg/kg) doses of CPhGs orally in long-term NIAAA model donors (FMT-EtOH-H). Network analysis and species distribution results demonstrated that Akkermansia and Allobaculum were the genera with the highest abundances in the gut microbiota and that their interaction was related to propionic acid metabolism. ConclusionsThe results suggest that CPhGs exert a protective effect against ALD by modulating the abundance and composition of Akkermansia and Allobaculum in the intestine, maintaining the intestinal mucus balance, and safeguarding intestinal barrier integrity.

Public Acceptance of Living Donor Liver Transplant for Colorectal Liver Metastases: A Web-Based Survey.

Recent advancements in cancer treatment and post-transplant management have expanded the population of living donor liver transplant (LDLT) candidates. We aimed to examine variations in public acceptance of LDLT based on patient diagnosis, including unresectable colorectal liver metastases (uCRLM). A web-based survey collected demographic information and general perceptions about organ donation in different settings. Respondents indicated their likelihood of being a living liver donor for a family member with genetic liver disease, alcohol-related liver disease (ALD), and uCRLM. Differences in the likelihood of donation between scenarios were compared. There were 491 survey respondents (female [76.5%], Caucasians [87.4%], and had at least a college degree [98.2%]). Most (82.4%) were aware of the option of living liver donation before the study and 95% supported living organ donation in general. Over 80% were registered as organ donors. Ninety percent indicated that they would be likely to donate to a family member with a genetic liver disease if they qualified as a living donor; significantly more than ALD (59%) and uCRLM (71%) (p < 0.001). Willingness to donate to patients with uCRLM was significantly higher (p < 0.001) than the hypothetical patient with ALD with a clinically accepted recovery period of 6 months. This study is the first of its kind to assess thepublic acceptance of living liver donation for uCRLM. Respondents were as or more supportive of donating to uCRLM as they were of generally accepted indications for LT. Further surveys with a broader respondent pool are warranted.

Serum immunoglobulin A levels: Diagnostic utility in alcoholic liver disease and association with liver fibrosis in steatotic liver disease.

The relationship between immunoglobulin A (IgA) levels and chronic liver disease remains poorly understood. The present study evaluated the clinical significance of IgA in 478 new patients who visited the Outpatient Clinic of Nagasaki Harbor Medical Center (Nagasaki, Japan). Serum IgA levels in comparison to liver stiffness (LS), as measured using a FibroScan® device, were evaluated in 358 patients. Furthermore, in 270 patients, the associations between serum IgA levels and body composition were analyzed using computed tomography. The IgA levels of patients in the groups with Child-Pugh classification B and C (CPGBC), alcoholic liver disease (ALD), steatotic liver disease (SLD) or diabetes were higher than the IgA levels of patients in the groups with CPGA, non-ALD, non-SLD or no diabetes, respectively. Logistic regression analysis showed that CPGBC, ALD, high IgG (>1,700 mg/dl), high macrophage galactose-specific lectin-2 binding protein glycosylation isomer (M2BPGi) (>1 cut-off index) and diabetes were contributing factors for high serum IgA level (>410 mg/dl). The ratio of IgA level divided by IgG level was highest in patients with ALD, followed by those with metabolic dysfunction-associated SLD (MASLD) and non-SLD. In SLD, IgA level was associated more with LS than M2BPGi and fibrosis-4 (FIB-4) in multiple regression analysis. In the receiver operating characteristic analysis, IgA level, M2BPG, and FIB-4 had similar area under the curve values for discriminating high LS (>8 kPa) from low LS (≤8 kPa) in SLD. IgA levels were also associated with visceral fat, and this association was only found in women. In conclusion, elevated IgA is an indicator of liver fibrosis that also reflects the presence of diabetes and an increased visceral fat level. Therefore, IgA is considered a useful marker of liver disease severity in the current era of increased SLD.

The Value of Liver Biopsy and Histology in Liver Disease Diagnosis and Patient Care-a Pragmatic Prospective Clinical Practice Study.

We aimed to examine the correlation of pre-biopsy clinical diagnosis with hepatic histopathology. Liver biopsy provides histologic information and informs physicians about the underlying clinical disease. We hypothesized that expert physicians' pre-biopsy clinical diagnoses may obviate the need for histopathological diagnosis. Patients undergoing liver biopsy to investigate a liver diagnosis were prospectively identified. In the 80 patients included, an anonymous validated questionnaire inquiring about the most likely clinical diagnosis and liver disease stage was completed prospectively by hepatologists before biopsy performance. The most common pre-biopsy diagnoses were alcoholic liver disease (19 diagnoses), followed by non-alcoholic steatohepatitis and autoimmune hepatitis (18 each). Overall, the predicted histologic diagnosis was the same as the histologic diagnosis in 51/80 patients (64%), and thus a new liver disease diagnosis was made in 36% of patients. The diagnosis with the greatest pre-biopsy and post-biopsy diagnosis discrepancy was autoimmune hepatitis, with the correct diagnosis being predicted in 6/18 (33%) of patients (other diagnoses included the following: non-alcoholic steatohepatitis/non-alcoholic fatty liver disease (4), alcoholic liver disease (3), drug-induced liver injury (3), others (2)). For fibrosis staging, when grouped as no fibrosis (F0), fibrosis (F1-F3), or cirrhosis (F4), the fibrosis stage was correctly predicted in 68% of patients (54/80). Notably, 7 patients (9%) who were initially thought to have no or early-stage fibrosis had F4 fibrosis, and 6/80 (8%) patients who were considered to have a liver disease diagnosis before their biopsy had normal histology. Although hepatology experts often predict the correct underlying liver disease diagnosis, histopathological diagnoses different from expected are common.

Lactobacillus helveticus attenuates alcoholic liver injury via regulation of gut microecology in mice.

Previous reports have demonstrated that alcohol consumption significantly reduces the abundance of Lactobacillus in the gut. In this study, we selected five species of the genus Lactobacillus, commonly found in fermented foods, and acknowledged them as safe, edible, and effective in preventing or treating certain diseases, to evaluate their effects on alcoholic liver disease (ALD). By comparing the liver damage indices in each group, we found that the type strain of Lactobacillus helveticus (LH, ATCC 15009) had the most marked alleviating effect on ALD-induced liver injury. Furthermore, experiments combining microbiomics and metabolomics were conducted to explore the mechanisms underlying the hepatoprotective effects of LH. Finally, we discovered that LH mitigated ethanol-induced liver steatosis and inflammation in ALD mice by altering the structure and function of the gut microbiome, increasing intestinal levels of short-chain fatty acids (SCFAs), and enhancing gut barrier integrity. These findings suggest a potential strategy for the clinical management of patients with ALD.

The association analysis between exposure to volatile organic compounds and fatty liver disease in US Adults

BackgroundLimited epidemiological research has explored the associations between ambient volatile organic compounds (VOCs) and fatty liver disease (FLD). This study aimed to explore the associations between VOCs and FLD and liver function biomarkers. We obtained urinary concentrations of VOCs metabolites from NHANES. MethodsWeighted logistic regression models were employed to investigate the relationships between VOCs and FLD risk, including alcoholic FLD (AFLD) and non-alcoholic FLD (NAFLD). The associations of VOCs and liver function biomarkers were also investigated using weighted linear regression. ResultsAmong the 2050 participants, 774 were classified as having FLD. After adjustment, each log-transformed SD increase in N-Acetyl-S-(2-carboxyethyl)-l-cysteine (CEMA), 2-Aminothiazoline-4-carboxylicacid (ATCA), and trans-trans-muconic-acid (MUCA) had a OR (95%CI) of 1.30 (1.06–1.61; P-trend=0.014), 1.34 (1.12–1.61; P-trend=0.002), and 1.22 (1.01–1.47; P-trend=0.035), respectively. ATCA and MUCA were associated with higher risks of NAFLD (OR=1.47, 95%CI: 1.20–1.79, and OR=1.26, 95%CI: 1.02–1.56, respectively). VOCs were positively associated with gamma glutamyl transaminase (GGT) and C-reactive protein (CRP), while inversely associated with albumin, total protein and alanine aminotransferase (ALT) (P < 0.05). ConclusionsUrinary metabolites of VOCs have been found to be strongly correlated with a higher risk of FLD and NFALD, and impaired liver function. These novel findings merit further prospective studies to comprehend the effect of VOCs on liver diseases.

Missed and Delayed Diagnoses of Chronic Liver Disease in Primary Care Patients with Cirrhosis.

Chronic liver diseases (CLD), cirrhosis, and hepatocellular carcinoma (HCC) cause significant morbidity and mortality. Unfortunately, patients with CLD often go undiagnosed until progression to cirrhosis and HCC. We aimed to determine the proportion of primary care patients with severe liver disease outcomes that had missed or delayed CLD diagnoses. This retrospective cohort study evaluated primary care patients with a diagnosis of cirrhosis, HCC, or other severe liver disease outcome between 2012 and 2021. The outcomes of interest were missed and delayed diagnoses of CLD, defined as the absence of a CLD diagnosis (missed) or first appearance of CLD on the same day as the cirrhosis diagnosis (delayed). Univariate analyses were performed to describe the cohort. Multivariable logistic regression models analyzed the association of aminotransferase elevations with the outcomes of interest. Of 667 patients with cirrhosis or HCC, 133 (20%) had a missed CLD diagnosis, and 243 (36%) had a delayed CLD diagnosis. Alcohol-related liver disease was the most common etiology among patients with missed/delayed diagnoses. A lower proportion of patients with missed/delayed diagnoses had an elevation in ALT or AST compared to patients with timely diagnoses (61% vs. 77%, p < 0.001). Elevated aminotransferase values were associated with lower odds of a missed/delayed diagnosis (OR 0.47; 95%CI 0.34-0.66). Most patients with cirrhosis or HCC had missed or delayed diagnoses of CLD in the context of probable overreliance on aminotransferase elevation for CLD detection. Enhanced screening for high prevalence CLD, especially alcohol, in primary care is needed.