Both alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease are leading contributors to chronic liver diseases. These conditions often coexist, exacerbating disease progression. Despite ALD being a leading cause of liver transplantation, many individuals with alcohol use disorder (AUD) do not receive treatment. In this review, we discussed the epidemiology of ALD in AUD, various treatment options for AUD, and their efficacy on liver health. Our critical analysis of current evidence underscores the need for integrated models involving multiple stakeholders to improve ALD management.

A multi-strain yeast-based paraprobiotic (MsYbP) comprising inactive cells and polysaccharides (β-glucan, mannan oligosaccharides, and oligosaccharides) derived from Saccharomyces cerevisiae and Cyberlindnera jadinii could ensure optimal growth and health in farmed fish. This study assessed the impact of an MsYbP on the growth, immune responses, antioxidant capacities, and liver health of largemouth bass (Micropterus salmoides) through lab-scale (65 days) and pilot-scale (15 weeks) experiments. Two groups of fish were monitored: one fed a control diet without the MsYbP and another fed 0.08% and 0.1% MsYbP in the lab-scale and pilot-scale studies, respectively (referred to as YANG). In the lab-scale study, four replicates were conducted, with 20 fish per replicate (average initial body weight = 31.0 ± 0.8 g), while the pilot-scale study involved three replicates with approximately 1500 fish per replicate (average initial body weight = 80.0 ± 2.2 g). The results indicate that the MsYbP-fed fish exhibited a significant increase in growth in both studies (p < 0.05). Additionally, the dietary MsYbP led to a noteworthy reduction in the liver function parameters (p < 0.05), such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AKP), and hepatic nuclear density, indicating improved liver health. Furthermore, the dietary MsYbP elevated the antioxidative capacity of the fish by reducing their malondialdehyde levels and increasing their levels and gene expressions related to antioxidative markers, such as total antioxidant ca-pacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), catalase (CAT), nuclear factor erythroid 2-related factor 2 (nrf2) and kelch-1ike ech-associated protein (keap1) in both studies (p < 0.05). In terms of hepatic immune responses, the lab-scale study showed an increase in inflammation-related gene expressions, such as interleukin-1β (il-1β) and transforming growth factor β1 (tgf-β1), while the pilot-scale study significantly suppressed the expressions of genes related to inflammatory responses, such as tumor necrosis factor α (tnfα) and interleukin-10 (il-10) (p < 0.05). In summary, our findings underscore the role of dietary multi-strain yeast-based paraprobiotics in enhancing the growth and liver health of largemouth bass, potentially through increased antioxidative capacity and the modulation of immune responses, emphasizing the significance of employing yeast-based paraprobiotics in commercial conditions.

The present study aimed to compare the nutritional effects of cholesterol, bile acids, and combination of cholesterol with bile acids in plant-based diets on juvenile genetically improved farmed tilapia (GIFT; Oreochromis niloticus). The isonitrogenous (321 g/kg crude protein) and isolipidic (76 g/kg crude fat) diets (Con diet) were based on plant protein sources, which included corn gluten meal, soybean meal, cottonseed meal and rapeseed meal. The Con diet was supplemented with 12 g/kg cholesterol (CHO diet), 0.2 g/kg bile acids (BAs diet), a combination of 12 g/kg cholesterol and 0.2 g/kg bile acids (CHO-BAs diet), respectively. Each diet was fed to three tanks in an indoor recirculating aquaculture system for 9 weeks. Results showed that compared to the Con group, fish had a higher weight gain rate, hepatosomatic index, and a lower feed conversion ratio in the CHO-BAs group. The highest levels of whole-fish fat and ash were found in the Con group. Serum parameters, including activities of alanine aminotransferase (ALT) and aspartate transaminase (AST), along with levels of glucose (GLU) and triglyceride (TG) except for total cholesterol (TCHO), were lower in the CHO, BAs, and CHO-BAs groups than those in the Con group (P < 0.001). Histological examination revealed that fish in the Con group exhibited severe hepatocyte vacuolization and diminished hepatocyte proliferation. Gene expression analysis indicated that the transcriptional levels of bile acid metabolism-related genes (including fxr, fgf19, bsep) were up-regulated in the CHO-BAs group (P < 0.05), whereas cholesterol metabolism-related genes (acly and hmgcr) were down-regulated in both CHO and CHO-BAs groups (P < 0.001). Moreover, UPLC-MS/MS analysis revealed that the higher taurine-conjugated bile acids (T-BAs), followed by free bile acids (Free-BAs) and glycine (G-BAs) were determined in tilapia bile. Among these, taurochenodeoxycholic bile acid was the predominant bile acid. Dietary bile acids supplementation also increased the proportion of T-BAs (tauro β-muricholic acid and taurodehydrocholic acid) while decreasing Free-BAs in the fish bile. In conclusion, the incorporation of cholesterol with bile acids into plant-based diets can effectively reduce cholesterol uptake, suppress bile acids synthesis, enhance bile acids efflux, and promote hepatocyte proliferation, which is helpful for maintaining the normal liver morphology in tilapia, and thus improving its growth performance.

This review explores the likely clinical impact of Pregnane X Receptor (PXR) activation by vitamin K on human health. PXR, initially recognized as a master regulator of xenobiotic metabolism in liver, emerges as a key regulator influencing intestinal homeostasis, inflammation, oxidative stress, and autophagy. The activation of PXR by vitamin K highlights its role as a potent endogenous and local agonist with diverse clinical implications. Recent research suggests that the vitamin K-mediated activation of PXR highlights this vitamin\'s potential in addressing pathophysiological conditions by promoting hepatic detoxification, fortifying gut barrier integrity, and controlling pro-inflammatory and apoptotic pathways. PXR activation by vitamin K provides an intricate association with cancer cell survival, particularly in colorectal and liver cancers, to provide new insights into potential novel therapeutic strategies. Understanding the clinical implications of PXR activation by vitamin K bridges molecular mechanisms with health outcomes, further offering personalized therapeutic approaches for complex diseases.

Chronic liver disease is a leading cause of death in the US and is often preventable. Rising burden, cost, and fatality due to liver disease are driven by intensified alcohol use in the US population and the contributions of comorbid conditions. This mini-review focuses on the topic of liver health in the context of chronic, behavioral cofactors of disease, using research-based examples from the Brown University Center for Addiction and Disease Risk Exacerbation (CADRE). Our aim is to illustrate the current challenges and opportunities in clinical research addressing liver health in the context of behavioral and medical comorbidity and to highlight next steps in this crucial area of public health research and clinical care.

BACKGROUND: Liver disease is among the leading causes of global mortality and morbidity. Given their substantial impact on public health, raising awareness about liver diseases is paramount for their prevention and effective management. This study aimed to evaluate the knowledge, awareness, attitudes, and behaviors of Syrians regarding liver health, chronic liver disorders, and their associated serious and irreversible complications.
METHODS: We conducted a cross-sectional study encompassing the adult Syrian population between August 25 and September 29, 2023, excluding non-Syrians and individuals below the age of 18 years. A validated questionnaire, adapted from a previous study, was employed, consisting of 31 questions that covered topics related to knowledge and awareness of liver health and diseases (3-point Likert scale), attitudes towards liver screening, diagnosis, and treatment, and awareness of treatment options and vaccination. Statistical analysis including logistic regression was conducted using Statistical Product and Service Solutions (SPSS, version 28; IBM SPSS Statistics for Windows, Armonk, NY), with statistical significance set established at pp-values below 0.05.
RESULTS: This study included 941 participants, with an average age of 26.5 years. While two-thirds of respondents demonstrated awareness of hepatitis B and C as viral diseases (663 (70.4%) and 612 (65.4%), respectively), approximately 66 (7%) were unaware of the potential for hepatitis to induce chronic liver inflammation or lead to liver failure. Over half of the participants were knowledgeable about the non-genetic nature of hepatitis B and C, and 579 (61.7%) were informed about the transmission risks associated with these infections. The most common reason cited for not participating in health screening tests was the perception of being in good health (219, 77.4%), and prescription medication was the most frequently sought treatment for hepatitis (543, 83.9%). Bivariate analysis revealed correlations between participant knowledge and sex, socioeconomic status, educational level, and occupation (P < 0.05). Similarly, the study identified significant associations between participant attitudes and age, gender, economic status, job, and educational level (P < 0.05). Moreover, the multivariate analysis demonstrated that gender, occupation, and educational level significantly influenced both participants\' knowledge and attitudes. Specifically, males exhibited lower knowledge and less favorable attitudes than females (P = 0.041 and P < 0.001, respectively).
CONCLUSIONS: The Syrian population possessed moderate knowledge of liver health and liver disorders. To bridge this knowledge gap and enhance preventive measures, it is recommended that additional health programs and awareness initiatives be implemented, involving healthcare providers and leveraging their expertise.

OBJECTIVE: This study investigated the effects of dietary supplementation with lysolecithins (LPC) on growth performance, nutrient digestibility, blood profiles, immunity, and liver health in broiler chickens.
METHODS: A cohort of 240 one-day-old male Arbor Acres broilers of comparable weight was divided into four treatment groups, each comprising six replicates of 10 birds. The groups were defined as follows: positive control with recommended metabolizable energy (PC+ME), negative control with 90 kcal/kg reduced ME (NC+ME), PC supplemented with 300 mg/kg LPC (PC+LPC), and NC supplemented with 300 mg/kg LPC (NC+LPC).
RESULTS: LPC supplementation led to a statistically significant reduction in the feed conversion ratio (p = 0.05) and a decrease in the proportion of abdominal fat and the liver (p<0.05). Digestibility of dry matter was also enhanced (p<0.05). Malondialdehyde concentrations in the liver were significantly reduced by LPC (p<0.01), with a noteworthy interaction between energy levels and LPC affecting this reduction (p<0.05). Serum levels of interleukin-6 were reduced on day 21, and both endotoxin and interleukin-6 levels were lower on day 42. Notably, a significant interaction was observed between the energy levels and LPC on relative liver weight and endotoxin concentrations in the serum (p<0.05).
CONCLUSIONS: The study concluded that LPC positively affects growth performance, nutrient digestibility, immune response, and antioxidative capacity in broiler chickens, affirming its value as a beneficial feed additive in poultry nutrition.

Berberine (BBR) and silymarin (SM) are natural compounds extracted from plants known for their antioxidant and chemoprotective effects on the liver. The present study aimed to investigate the beneficial properties of BBR and SM and the association of BBR with SM on liver function using fish as \"in vivo\" models. Moreover, the study investigated their hepatoprotective role after acetaminophen (APAP) exposure. For this purpose, the fish (N = 360; 118.4 ± 11.09 g) were fed with control or experimental diets for 9 weeks. In the experimental diets, the feed was supplemented with either SM (1 g/kg feed), BBR (100 and 200 mg/kg feed), or a combination of BBR with SM (SM 1 g/kg feed + BBR 100 mg/kg feed and, respectively, SM 1 g/kg feed + BBR 200 mg/kg feed). After the feeding trial, seven fish from each tank were randomly selected and exposed to a single APAP dose. The selected serum biochemical markers, oxidative stress markers, and lysozyme activity were used to evaluate the efficiency of the supplements on carp\'s health profile, particularly regarding the hepatopancreas function. Our results showed that the inclusion of SM and BBR (either as a single or in combination) reduced the serum contents of total cholesterol, triglyceride, and alanine transaminase. An increase in the high-density cholesterol was observed after the administration of BBR or BBR in association with SM. Both supplements showed hepatoprotective activity against APAP-induced hepatotoxicity, especially BBR. The ameliorative effects of SM (1 g) in association with BBR (100 mg) were highlighted by the modulation of the nonspecific immune system and oxidative stress alleviation after APAP exposure.

The hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatus) is a new species of grouper crossed from giant grouper (E. lanceolatus) as the male parent and brown-marbled grouper (E. fuscoguttatus) as the female parent. We hypothesized that optimal levels of dietary protein may benefit liver function. High-lipid diets are energetic feeds that conserve protein and reduce costs, and are a hot topic in aquaculture today. Therefore, the objective of the research is to investigated the effects of dietary protein level in high-lipid diets on serum and liver biochemistry, liver histology, and liver immune and antioxidant indexes and gene mRNA expression of the juvenile hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatus). Six iso-lipidic (161 g/kg) diets were formulated containing graded levels of protein (510 as control, 480,450, 420, 390 and 360 g/kg). Each treatment consisted of three replicates and 30 fish (6.70 ± 0.02 g) in one replicate. After an 8-week feeding experiment, the results indicated the following: (1) With the decreasing of dietary protein level, the specific growth rate (SGR) of groupers increased gradually and then decreased; SGRs of the 390 and 360 g/kg groups were significantly lower than other groups (p < 0.05). (2) In terms of serum and liver, the activity of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD), and the total antioxidant capacity (T-AOC) content, and the activity of immune enzymes such as lysozyme (LYS) and immunoglobulin (IgM) was significantly increased under the appropriate protein level. (3) Based on liver histology, we know that high or low dietary protein levels cause liver damage. (4) Dietary protein levels can significantly affect the mRNA expression levels of an anti-inflammatory factor gene (tgfβ), pro-inflammatory factor genes (il6, il8), heat shock proteins, and antioxidant and immune genes (hsp70 and hsp90, gpx, nrf2, keap1). It is concluded that the appropriate protein level can promote the growth performance of groupers, improve antioxidant activity and immune enzyme activity in serum and liver, and enhance the expression of immune genes.

This study evaluated the effects of feeding an ultra-diluted complex to dairy cows during the transition period and early lactation. Thirty multiparous pregnant dairy cows were blocked and randomly assigned to either a placebo control (CON) group or ultra-diluted complex (UD) group. The CON group received a placebo (basal diet + 40 g/cow/day of expanded silicate), while the UD group received the ultra-diluted complex (basal diet + 40 g/cow/day of PeriParto Transição-RealH, composed of ultra-diluted substances + vehicle: expanded silicate). Cows were evaluated from 30 days before the expected calving date until 60 days in milk (DIM) for sample and data collection. Post-partum dry matter intake (DMI) was not affected by the treatment. Cows fed UD had higher DMI relative to BW. Feeding UD increased milk lactose content and decreased milk protein content. Cows fed UD had lower somatic cell counts in the third and fourth week of lactation. Cows fed UD showed a tendency for higher liver health index. Using UD during the transition period and early lactation may benefit liver and udder health of dairy cows with no detrimental effect on milk performance.