Alcohol is a molecule whose multiple effects in living organisms exemplify how profound biological complexity can arise from an exceptionally simple chemical structure interacting with the cellular biochemical machinery. This review was conceived to provide an up-to-date synthesis of the current knowledge on the multifaceted consequences of alcohol oxidative metabolism and alcohol-derived oxidative stress, ranging from disruption of subcellular and cellular homeostasis to impairment of organ function. This study primarily focuses on the consequences of alcohol metabolism and on the mechanisms by which the rise of its main metabolite, acetaldehyde, and of reactive oxygen species (ROS), generates oxidative stress by-products and molecular adducts responsible for compromising cellular energy balance and antioxidant defense mechanisms. In particular, this review aims to provide an exhaustive representation of the mechanisms, causes, and consequences of alcohol oxidative metabolism: this is accomplished by taking into account alcohol-induced modifications of gene expression of cellular antioxidant determinants, the role of epigenetic mechanisms, and that of gene polymorphisms linked to alcohol-dependent oxidative stress and responsible for serious diseases such as, among others, alcoholic hepatitis, cirrhosis, and hepatocellular carcinoma. In addition, this review highlights the role of alcohol oxidative metabolism in the brain, which, in the acute setting, activates the dopaminergic system mainly involved in alcohol reinforcing properties and, upon chronic exposure, contributes to neurodegenerative disorders. Finally, a dedicated paragraph explores autophagy as an integrative mechanism underlying the effects of alcohol-related oxidative stress across multiple organs, including the liver, heart, and brain.

Alcohol-associated hepatitis, the new term that has replaced "alcoholic hepatitis", is the most severe form of alcohol-related liver disease, with a 1-month mortality of 30 to 50% in severe cases. The diagnosis is now mainly clinical, with liver biopsy reserved for atypical presentations. The MELD (Model for End-Stage Liver Disease) 3.0 and the Lille score calculated from day 4 allow for dynamic prognostic stratification. In eligible patients, prednisolone at a dose of 40 mg/day for 28 days remains the standard treatment. Nutritional and addiction management are major determinants of survival, while early liver transplantation, without an arbitrary abstinence period, is a rescue option for carefully selected non-responders.

Hepatoprotection of Apocynum venetum flavonoids: Targeting oxidative stress via coordinated NRF2/BCHE induction and AR inhibition.

COLEC10 and COLEC11 are presumed to act as pattern recognition receptors to activate the complement system by binding to MASP1. However, it is not clear whether the serum concentrations of COLEC10, COLEC11 and MASP1 can be diagnostic markers of chronic liver disease (CLD). This study aimed to investigate the diagnostic value of serum concentrations of COLEC10, COLEC11 and MASP1 in CLD. The study included 17 healthy donors and 128 patients who were diagnosed with chronic liver disease. The serum concentrations of COLEC10, COLEC11 and MASP1 were measured with ELISA kits. The clinical data of the patients were collected and analyzed. The serum concentrations of COLEC10 and COLEC11 are significantly increased in the patients with CLD. However, the serum concentration of MASP1 did not show a significant change in patients with CLD. The univariate correlation analysis reveals that the serum concentrations of COLEC10, COLEC11 and MASP1 are not strongly correlated with other clinical markers. Subgroup analysis based on the etiology of chronic liver disease demonstrates that the serum concentrations of COLEC10 and COLEC11 are increased in patients with viral hepatitis, autoimmune hepatitis, and alcoholic hepatitis, but not in metabolic dysfunction-associated steatotic liver disease, whereas MASP1 is only increased in patients with alcoholic hepatitis. The serum concentrations of COLEC10, COLEC11 and MASP1 are increased in patients with liver cirrhosis. This study demonstrates that the serum concentrations of COLEC10 and COLEC11 are new biomarkers of chronic liver disease characterized by liver fibrosis and an advanced-stage phenotype. Further studies are needed to confirm the clinical value of serum concentrations of COLEC10 and COLEC11 in the diagnosis and prognosis of chronic liver disease.

Current Therapeutic Targets for Alcohol-Associated Liver Disease.

Geographic Differences in Transplantation Among Patients with Acute Alcoholic Hepatitis

Gut microbiota and nutritional interventions in alcohol-associated liver disease: Mechanisms and therapeutic advances.

Abstract Background Menopausal hormone therapy (MHT) has been investigated for its potential influence on risks of oesophageal, gastric, and primary liver cancers, but evidence remains inconclusive. This study aimed to evaluate associations between MHT use and these cancers using a large, nested case-control design. Method Using the UK Clinical Practice Research Datalink (CPRD) linked with National Cancer Registration and Analysis Service data, we conducted nested case-control studies assessing MHT exposure and risks of oesophageal, gastric, and primary liver cancers in female patients. Users were defined in a hierarchial fashion as oestrogen-only, oestrogen-and-progesterone, or tibolone (an oestrogen analogue) users. Multivariable logistic regression models adjusted for confounders including smoking, alcohol, comorbidities, and viral hepatitis status. Sensitivity analyses included extended lag periods and multiple imputation for missing data. Results A total of 5,225 cases matched to 50,599 controls across the three cancer sites were evaluated. MHT use was associated with a 15% decreased risk of oesophageal cancer (adjusted OR=0.85, 95% CI 0.72, 1.00, p=0.048,) and a 33% decreased risk of primary liver cancer (adjusted OR=0.67, 95% CI 0.49, 0.92, p=0.01). A dose-response relationship was suggested for primary liver cancer in a test for trend but was not statistically significant. Oestrogen-only MHT users showed a stronger protective association for primary liver cancer. No protective effect was found for gastric cancer. Histological subtype analyses showed no significant associations. Sensitivity analyses supported the robustness of findings. Conclusions These findings support a protective effect of systemic MHT, particularly oestrogen-only formulations, on oesophageal and primary liver cancer risk, but not gastric cancer.

Sarcopenia is a frequent and prognostically significant complication of liver cirrhosis. Hand grip strength (HGS) has emerged as a simple, noninvasive tool for assessing muscle function, yet limited data exist on its utility in Indian cirrhotic populations. To evaluate the association of HGS with established prognostic scores and biochemical parameters in Indian patients with cirrhosis. In this cross-sectional observational study, 100 adult cirrhotic patients were assessed between August 2022 and December 2023. HGS was measured using a validated hand-held dynamometer. Correlations between HGS and clinical scores of severity of cirrhosis [Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD)] and biochemical markers were analyzed using appropriate statistical methods. Mean patient age was 59.2 ± 8.46 years; 85% were male. The most common etiologies were alcohol (46%) and viral hepatitis (26%). HGS declined significantly with increasing liver disease severity: CTP A (34.0 ± 1.48 kg), B (21.63 ± 1.07 kg), and C (13.5 ± 2.87 kg) (p < 0.0001). HGS was inversely correlated with MELD score (r = -0.820) and showed strong positive correlations with serum albumin (r = +0.872) and hemoglobin (r = +0.59). Age, international normalized ratio (INR), and bilirubin were negatively correlated with HGS. HGS is strongly associated with liver disease severity and key biochemical indicators. As a bedside, radiation-free tool, it offers a practical method for assessing sarcopenia in cirrhosis, especially in resource-limited settings.

Although probiotics are considered a possible treatment for alcoholic liver disease (ALD), their effectiveness in enhancing liver function in patients with ALD is still unclear. In this investigation we sought to determine the influence of probiotics on liver function markers in patients with ALD. with a focus on the efficacy of alanine aminotransferase (ALT). We also examined aspartate aminotransferase (AST), total bilirubin (TB), albumin (ALB), and gamma-glutamyl transferase (GGT). Through systematic searches of medical databases, including Web of Science, PubMed, Embase, Cochrane Library, Ovid, and Wan Fang, we identified 15 randomized controlled trials involving patients with alcoholic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Probiotic therapy significantly reduced levels of ALT (standard mean difference [SMD], -0.50; 95% CI, -0.86 to -0.14; P = .007) and AST (SMD, -0.26; 95% CI, -0.52 to 0.00; P = .05). No significant effects were observed on TB (SMD, -0.90; 95% CI, -1.06 to 0.13; P = .12), ALB (SMD, 0.16; 95% CI, -0.06 to 0.37; P = .15), or GGT (SMD, 0.14; 95% CI, -0.11 to 0.40; P = .26) levels. Regional disparities were noted, with Asian patients showing a significant reduction in ALT levels. Patients undergoing treatments lasting 8 weeks or more also showed significant reductions in ALT levels. Furthermore, in this review we identified a more pronounced effect on ALT level reduction in subgroups with a higher proportion of male participants. According to this meta-analysis, administration of probiotics could assist in managing ALT levels in ALD patients, offering a novel approach to ALD treatment. PROSPERO registration No. CRD42024619024.

Preventable liver cancer cases through reduced exposure to overweight/obesity, alcohol consumption, tobacco use, and hepatitis B infection

Around 2.3 billion people globally consume alcohol, with Europe leading at 9.8 litres per capita. This high level of alcohol consumption significantly contributes to liver diseases, including alcoholic hepatitis, cirrhosis, and liver cancer. This review explores alcohol consumption's impact on liver function, focusing on alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) levels to understand liver health, disease progression, and influencing factors. The study used multiple databases and manual searches, with eligibility criteria including original research articles from diverse demographics and regions. Two independent reviewers conducted the screening process, minimizing bias and enhancing reliability. The Joanna Briggs Institute's critical appraisal checklist assessed the quality and risk of bias in the studies. Meta-Mar v3.5.1 was used for data analysis, with descriptive statistical tests and a random-effects model to synthesize findings across studies. Subgroup analyses were conducted to explore regional variations. The meta-analysis, incorporating data from 27 datasets across 13 studies, demonstrated a significant overall risk of alcohol consumption impacting liver function tests (LFTs). The pooled relative risk (RR) was 1.33 (95% CI: 0.97–1.82), as determined using a random-effects model (z/t = 1.86, p = 0.007). Higgins' I² statistic was extremely high at 99.4% (95% CI: 99.4%–99.5%), with an H value of 13.23 (95% CI: 12.49–14.01), confirming substantial heterogeneity (Q = 4550.29, df = 26, p = 0). The findings revealed that alcohol consumption increases the relative risk of elevated liver enzyme levels: ALT had a RR of 1.2625 (95% CI: 0.8459–1.8842), AST had an RR of 1.1783 (95% CI: 0.4851–2.8621), and GGT had a RR of 1.7645 (95% CI: 0.8241–3.7782). The observed outcomes regarding the effects of alcohol consumption on ALT, AST, and GGT were not significantly influenced by publication bias, as confirmed by Egger's regression analysis with no significant publication bias (t = 0.06, df = 25, p = 0.9558). Alcohol consumption negatively impacts LFTs, leading to elevated levels of key enzymes like ALT, AST, and GGT. This risk is consistent across geographical areas, suggesting the need for consideration in assessing alcohol's impact on liver health.

AVERAGE AMOUNT OF ALCOHOL INTAKE IN PATIENTS ADMITTED WITH ALCOHOLIC HEPATITIS IN INDIA: A RETROSPECTIVE STUDY

Disrupting liver immune homeostasis drives inflammation. Recent evidence shifts immunoregulatory focus to hepatocytes, though the mechanisms remain poorly defined. Forkhead box O1 (FoxO1) is a critical homeostasis regulator, but its function in liver immune homeostasis is unknown. We aimed to clarify the role of hepatocyte FoxO1 in liver immune homeostasis and inflammation. Human liver FoxO1 expression and its association with inflammation were analyzed in patients with various inflammation-related liver diseases. Hepatocyte-specific Foxo1 knockout (FoxO1 △hepa ) mice were established. Hepatocyte-specific gene interference was employed in alcoholic hepatitis and hepatic schistosomiasis murine models. Transcriptomic, single-cell RNA sequencing, and CUT&Tag analyses were performed to elucidate the underlying mechanisms. Hepatocyte FoxO1 levels in human inflammatory livers declined prevalently and were inversely correlated with inflammation and fibrosis. Around 15-18 weeks after birth, FoxO1 △hepa mice exhibited mild spontaneous hepatic inflammation with natural killer T (NKT) cell and neutrophil accumulation. NKT cell depletion in FoxO1 △hepa mice with alcoholic hepatitis or hepatic schistosomiasis (HS) significantly reduced neutrophil accumulation and protected against liver inflammation and damage. Mechanistically, FoxO1 promoted retinoic acid synthesis to induce hepatocyte CD1d expression, which is necessary for regulating NKT cell apoptosis. Innovatively, decreased JMJD1C expression in hepatocytes caused histone H3 lysine 9 (H3K9) dimethylation at the Foxo1 promoter, repressing its transcription and disrupting local immune homeostasis. Our findings uncover a hitherto unrecognized mechanism for hepatocyte-based control of liver inflammation, in which hepatocyte FoxO1 maintained by JMJD1C restrains local NKT cells and neutrophils via CD1d induction, providing promising targets for inflammatory liver diseases.

Introduction . Synthesized in the 1950s, ursodeoxycholic acid (UDCA) is a highly effective hepatoprotective drug. UDCA is well known for its pleiotropic properties with litholytic, hypocholestatic, immunomodulatory, antiapoptotic and other effects. The purpose of the work is to discuss the pharmacological effects of UDCA and its clinical use in the most common liver and gallbladder diseases. Materials and methods . This is a narrative review of the most relevant national and foreign publications focused on UDCA. The literature search was performed in PubMed, eLibrary.ru and printed sources from 1981 to 2025. Results and discussion . Multitarget prophylactic and therapeutic action of UDCA includes hepatoprotective effect in viral and alcoholic hepatitis, improvement of clinical and laboratory parameters in cholestasis, a decrease in cholesterol levels in non-alcoholic fatty liver disease, a litholytic effect in biliary sludge and cholelithiasis, and a potential ability to prevent cancer of the liver and the entire digestive tract. Conclusion . UDCA has a broad spectrum of the beneficial effects in hepatobiliary and concomitant cardiometabolic pathology. Multitarget action together with high safety profile allow the drug to be widely used in the treatment of comorbid gastroenterological patients.

IntroductionAbdominal paracentesis is a commonly performed diagnostic and therapeutic procedure for the management of ascites, most often associated with liver cirrhosis and alcoholic hepatitis (LCAH). Understanding how its use in the emergency department (ED) has changed over time can help optimize resource allocation and patient care. This study used National Emergency Department Sample (NEDS) data to describe temporal trends in ED presentations for LCAH and associated abdominal paracenteses in the United States from 2012 to 2021.MethodsWe conducted a retrospective observational study of adult ED encounters in NEDS between 2012 and 2021. Encounters with a primary or secondary diagnosis of LCAH were identified using International Classification of Diseases (ICD)-9-CM and ICD-10-CM diagnosis codes. Abdominal paracenteses were identified using corresponding procedure codes. We quantified (1) annual numbers and rates of ED visits with LCAH and abdominal paracentesis relative to all ED visits, (2) distributions of three clinical subgroups of LCAH patients with major clinical complications (CirMCC), clinical comorbidities (CirCC), or without complications/comorbidities (CirWC), and (3) annual proportions of LCAH encounters undergoing versus not undergoing paracentesis.ResultsFrom 2012 to 2021, there were 214,412 ED encounters with LCAH and 51,683 abdominal paracenteses. The rate of LCAH among all ED visits increased from 0.0030% in 2012 to 0.0287% in 2021, and the rate of abdominal paracentesis among all ED visits rose from 0.0017% to 0.0071% over the same period. Among patients with LCAH, the proportion undergoing paracentesis decreased over time, from 56.9% in 2012 to 24.8% in 2021. CirMCC remained the largest subgroup across the study period, while CirCC and CirWC comprised smaller but relatively stable proportions.ConclusionAcross a decade of NEDS data, LCAH-related ED visits and absolute numbers of abdominal paracenteses increased, while the proportion of LCAH patients undergoing paracentesis declined. CirMCC, CirCC, and CirWC subgroups maintained stable relative frequencies. These findings suggest evolving patterns in the ED management of liver disease-related ascites and highlight the importance of anticipating procedural demand, staffing needs, and preventive strategies for liver disease.

miR-148a promotes the expression of multiple alcohol dehydrogenase genes by activating an ADH4 enhancer element.

Background: Periodontal dysbiosis contributes to liver injury through systemic inflammation, oral-gut microbial translocation, and endotoxemia. Lipopolysaccharides (LPSs) and virulence factors derived from periodontal pathogens, particularly Porphyromonas gingivalis (P. gingivalis) activate Toll-like receptor (TLR) signaling, trigger NF-κB-mediated cytokine release (e.g., TNF-α, IL-1β, IL-6), and promote oxidative stress and Kupffer cell activation within the liver. The present systematic review summarized clinical evidence supporting these mechanistic links between periodontal pathogens and hepatic outcomes, highlighting the role of microbial crosstalk in liver pathophysiology. Methods: A PRISMA-compliant systematic review was conducted by searching PubMed, Scopus, and the Cochrane library, as well as gray literature. Eligible study designs were observational studies and trials evaluating P. gingivalis and other periodontal pathogens (Aggregatibacter actinomycetemcomitans, Prevotella intermedia, and Tannerella forsythia) for liver phenotypes (Non-Alcoholic Fatty Liver Disease [NAFLD]/Metabolic Dysfunction-Associated Steatotic Liver Disease [MASLD], fibrosis/cirrhosis, acute alcoholic hepatitis [AAH], and Hepatocellular carcinoma [HCC]). Risk of bias was assessed using the Newcastle-Ottawa Scale adapted for cross-sectional studies (NOS-CS) for observational designs and the RoB 2 scale for single randomized controlled trials (RCTs). Due to the heterogeneity of exposures/outcomes, results were summarized narratively. Results: In total, twenty studies (2012-2025; ~34,000 participants) met the inclusion criteria. Population-level evidence was conflicting (no clear association between anti-P. gingivalis serology and NAFLD), while clinical cohorts more frequently linked periodontal exposure, particularly to P. gingivalis, to more advanced liver phenotypes, including fibrosis. Microbiome studies suggested stage-related changes in oral communities rather than the effect of a single pathogen, and direct translocation into ascitic fluid was not observed in decompensated cirrhosis. Signals from interventional and behavioral research (periodontal therapy; toothbrushing frequency) indicate a potential modifiability of liver indices. The overall methodological quality was moderate with substantial heterogeneity, precluding meta-analysis. Conclusions: Current evidence supports a biologically plausible oral-liver axis in which periodontal inflammation, often involving P. gingivalis, is associated with liver damage. Causality has not yet been proven; however, periodontal evaluation and treatment may represent a low-risk option in periodontitis-associated NAFLD. Well-designed, multicenter prospective studies and randomized trials with standardized periodontal and liver measurements are needed.

Chronic liver disease is the leading cause of non-HIV-related mortality in women with HIV (WWH). We review the pathophysiology of liver injury in WWH, natural history and management of common liver diseases, and role of viral, pharmacologic, and sex hormone-related factors in exacerbating liver disease progression in WWH. In the current era of effective antiretroviral therapy (ART), viral hepatitis related liver disease has decreased in prevalence, while alcohol-associated and metabolic dysfunction associated steatotic liver disease (MASLD) have become more common. Several mechanisms cause accelerated fibrogenesis in WWH, including direct cytopathic effects from HIV, ART, gastrointestinal barrier impairments, and microbiome alterations. The menopausal transition is a critical period in which WWH develop a profibrogenic state exacerbated by HIV-associated estrogen deficiency. Glucagon-like peptide-1 use in WWH holds promise in reversing hepatic steatosis. Higher rates of hazardous alcohol use and psychiatric comorbidities in WWH, compared to men with HIV, increases the risk of alcohol and viral hepatitis related liver disease. WWH experience unique challenges to achieving optimal liver disease care due to social marginalization, biological sex differences, and HIV infection itself. Future research investigating mechanisms and potential interventions is needed to improve liver health outcomes in this high-risk population.

BackgroundTo evaluate the therapeutic effects of entecavir combined with reduced glutathione on serum type III procollagen (PCIII), plasma procollagen V (IVC), Tumour Necrosis Factor-a (TNF-a), interleukin-6 (IL-6), and nutritional status in patients with hepatitis B complicated by alcoholic liver cirrhosis.MethodsThis study included 92 patients with alcoholic liver cirrhosis and hepatitis B, treated between April 2022 and January 2024. Patients were randomised into two groups: group A received 0.5 mg of entecavir daily, and group B received 0.5 mg of entecavir daily plus 0.3 g of reduced glutathione 1-2 times per day for 2 months. Nutritional parameters, inflammatory markers, liver function, and malnutrition were compared between groups. Statistical analysis was performed using SPSS12.0, with independent t-tests for group comparisons and x2 tests for categorical data. A P-value <0.05 was considered statistically significant.ResultsGroup B showed a higher effective treatment rate (97.82%) compared to group A (76.08%). Malnutrition improved significantly more in group B. After treatment, group B exhibited more significant reductions in BMI, TSF, AMC, PA, Hb, ALB, TNF-a, CRP, IL-6, TBIL, AST, ALT, HA, PCIII, and IVC than group A.ConclusionsEntecavir combined with reduced glutathione improves liver function and nutritional status and reduces inflammatory markers in patients with hepatitis B and alcoholic liver cirrhosis, demonstrating high safety and effectiveness.