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Portal hypertension (PH) is a complex clinical challenge with severe complications, including variceal bleeding, ascites, hepatic encephalopathy, and hepatorenal syndrome. The gut microbiota (GM) and its interconnectedness with human health have emerged as a captivating field of research. This review explores the intricate connections between the gut and the liver, aiming to elucidate how alterations in GM, intestinal barrier function, and gut-derived molecules impact the development and progression of PH. A systematic literature search, following PRISMA guidelines, identified 12 original articles that suggest a relationship between GM, the gut–liver axis, and PH. Mechanisms such as dysbiosis, bacterial translocation, altered microbial structure, and inflammation appear to orchestrate this relationship. One notable study highlights the pivotal role of the farnesoid X receptor axis in regulating the interplay between the gut and liver and proposes it as a promising therapeutic target. Fecal transplantation experiments further emphasize the pathogenic significance of the GM in modulating liver maladies, including PH. Recent advancements in metagenomics and metabolomics have expanded our understanding of the GM's role in human ailments. The review suggests that addressing the unmet need of identifying gut–liver axis-related metabolic and molecular pathways holds potential for elucidating pathogenesis and directing novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-alcoholic fatty liver disease affects up to a quarter of the adult population in many developed and developing countries. This disease has become the fastest-growing cause of hepatocellular carcinoma (HCC) in industrialized countries. The annual incidence of hepatocarcinoma varies between patients with cirrhosis and noncirrhotic patients. In this review, HCC associated with non-alcoholic fatty liver disease will be described, considering its epidemiology, risk factors, and management, including preventive strategies and therapeutic approaches. Non-alcoholic fatty liver disease (NAFLD) affects up to a quarter of the adult population in many developed and developing countries. This spectrum of liver disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. The incidence of NASH is projected to increase by up to 56% over the next 10 years. There is growing epidemiological evidence that NAFLD has become the fastest-growing cause of hepatocellular carcinoma (HCC) in industrialized countries. The annual incidence of HCC varies between patients with NASH cirrhosis and patients with noncirrhotic NAFLD. In this review, NAFLD/NASH-associated HCC will be described, including its epidemiology, risk factors promoting hepatocarcinogenesis, and management of HCC in patients with obesity and associated metabolic comorbidities, including preventive strategies and therapeutic approaches to address this growing problem. [ABSTRACT FROM AUTHOR]

HCV infection is still a major burden worldwide, and most countries are not on track to meet the WHO 2030 elimination goal. The current challenge is to identify individuals to be treated. In this study, we will describe the trend of new DAA prescriptions and the changes over time in terms of the characteristics of patients starting antiviral therapy in our unit. Data of 1646 hepatitis C patients who started therapy during the period of 2015–2022 regarding annual number of prescriptions, age, gender, nationality, HCV genotype, provenance, and liver disease severity were analyzed. We observed a peak in the number of new prescriptions in 2018 and a downward trend starting in 2019. Patients from the general population, centers for addictions, and prison differed significantly. The mean age in the general population remained above 60 years, the percentage of patients from centers for addictions and prison increased and, after 2016, there was no significant change in the percentage of patients with F3–F4 fibrosis. As HCV screening and linkage-to-care pathways seem to be already well implemented and successful in centers for addictions and in prisons, efforts need to be focused on those of older age in the general population. To carry this out, the more structured involvement of different health professionals must be figured out. [ABSTRACT FROM AUTHOR]

There are very few reports about the intake of nutrients for the development or progression of non-alcoholic steatohepatitis (NASH). The aim of this study was to identify the dietary habits and the nutrient intake in patients with NASH, in comparison to chronic hepatitis C (HCV)-related patients. We prospectively evaluated the intake of macronutrients and micronutrients in 124 NAFLD and 162 HCV patients, compared to 2326 subjects as a control group. We noticed major differences in macro- and micronutrients intakes in NASH and HCV patients compared to controls. Proteins, carbohydrate (glucose, fructose, sucrose, maltose and amide), saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), folic acid, vitamin A and C (p < 0.0001), and thiamine (p < 0.0003) ingestion was found to be higher in patients with NASH, while total lipids, polyunsaturated fatty acid (PUFA), riboflavin and vitamin B6 daily intake were lower compared to controls (p < 0.0001). Similarly, NASH patients had significantly reduced carbohydrate intake (p < 0.0001) and an increased intake of calcium (p < 0.0001) compared to HCV positive patients. Finally, we showed in NASH males an increase in the intake of SFA, PUFA, soluble carbohydrates (p < 0.0001) and a decrease in the amount of fiber (p < 0.0001) compared to control males. In NASH female population, we showed an increase of daily total calories, SFA, MUFA, soluble carbohydrates, starch and vitamin D ingested (p < 0.0001) with a reduction of fibers and calcium (p < 0.0001) compared to control females. This study showed how NASH patients' diets, in both male and females, is affected by a profound alteration in macro- and micronutrients intake. [ABSTRACT FROM AUTHOR]

Metabolic- (dysfunction) associated fatty liver disease (MAFLD) represents the predominant hepatopathy and one of the most important systemic, metabolic-related disorders all over the world associated with severe medical and socio-economic repercussions due to its growing prevalence, clinical course (steatohepatitis and/or hepatocellular-carcinoma), and related extra-hepatic comorbidities. To date, no specific medications for the treatment of this condition exist, and the most valid recommendation for patients remains lifestyle change. MAFLD has been associated with metabolic syndrome; its development and progression are widely influenced by the interplay between genetic, environmental, and nutritional factors. Nutrigenetics and nutrigenomics findings suggest nutrition's capability, by acting on the individual genetic background and modifying the specific epigenetic expression as well, to influence patients' clinical outcome. Besides, immunity response is emerging as pivotal in this multifactorial scenario, suggesting the interaction between diet, genetics, and immunity as another tangled network that needs to be explored. The present review describes the genetic background contribution to MAFLD onset and worsening, its possibility to be influenced by nutritional habits, and the interplay between nutrients and immunity as one of the most promising research fields of the future in this context. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) represents the result of hepatic fat overload not due to alcohol consumption and potentially evolving to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Fructose is a naturally occurring simple sugar widely used in food industry linked to glucose to form sucrose, largely contained in hypercaloric food and beverages. An increasing amount of evidence in scientific literature highlighted a detrimental effect of dietary fructose consumption on metabolic disorders such as insulin resistance, obesity, hepatic steatosis, and NAFLD-related fibrosis as well. An excessive fructose consumption has been associated with NAFLD development and progression to more clinically severe phenotypes by exerting various toxic effects, including increased fatty acid production, oxidative stress, and worsening insulin resistance. Furthermore, some studies in this context demonstrated even a crucial role in liver cancer progression. Despite this compelling evidence, the molecular mechanisms by which fructose elicits those effects on liver metabolism remain unclear. Emerging data suggest that dietary fructose may directly alter the expression of genes involved in lipid metabolism, including those that increase hepatic fat accumulation or reduce hepatic fat removal. This review aimed to summarize the current understanding of fructose metabolism on NAFLD pathogenesis and progression. [ABSTRACT FROM AUTHOR]

Many studies have shown that resveratrol has a lot of therapeutic effects on liver disorders. Its administration can significantly increase the survival rate after liver transplantation, reduce fat deposition and ischemia-induced necrosis and apoptosis in Wistar rats. Resveratrol can provide Liver protection against chemical, cholestatic, and alcohol-mediated damage. It can improve glucose metabolism and lipid profile, reduce liver fibrosis, and steatosis. Additionally, it is capable of altering the fatty acid composition of the liver cells. Resveratrol may be a potential treatment option for the management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant, and calorie-restricting effects. There are also studies that have evaluated the effect of resveratrol on lipid and liver enzyme profiles among patients with metabolic syndrome (MetS) and related disorders. Based on the extent of liver disease worldwide and the need to find new treatment possibilities, this review critically examines current in vitro and in vivo preclinical studies and human clinical studies related to liver protection. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection remains a pressing public health issue. Our aim is to assess the linkage to care of patients with HCV diagnosis and to support the proactive case-finding of new HCV-infected patients in an Italian primary care setting. This was a retrospective cohort study of 44 general practitioners (GPs) who managed 63,955 inhabitants in the Campania region. Adults with already known HCV diagnosis or those with HCV high-risk profile at June 2019 were identified and reviewed by GPs to identify newly diagnosed of HCV and to assess the linkage to care and treatment for the HCV patients. Overall, 698 HCV patients were identified, 596 with already known HCV diagnosis and 102 identified by testing the high-risk group (2614 subjects). The 38.8% were already treated with direct-acting antivirals, 18.9% were referred to the specialist center and 42.3% were not sent to specialist care for treatment. Similar proportions were found for patients with an already known HCV diagnosis and those newly diagnosed. Given that the HCV infection is often silent, case-finding needs to be proactive and based on risk information. Our findings suggested that there needs to be greater outreach, awareness and education among GPs in order to enhance HCV testing, linkage to care and treatment. [ABSTRACT FROM AUTHOR]