The article discusses the progression and management of cirrhosis, emphasizing the importance of precise disease staging from compensated to decompensated states. This article evaluates the roles of beta-blockers, albumin, and rifaximin, emphasizing their potential as disease-modulating agents. By exploring these therapeutic strategies within clinical and research frameworks, the article reinforces the necessity for innovative treatments that can fundamentally alter the natural course of cirrhosis and improve patient outcomes.

Alcohol consumption remains a significant contributor to liver-related morbidity and mortality worldwide. This review explores the interplay between alcohol use and various liver conditions including viral hepatitis, hereditary hemochromatosis and secondary iron overload, autoimmune liver diseases, and rare disorders such as Wilson's disease, Fontan-associated liver disease, alpha-1 antitrypsin, noncirrhotic portal hypertension, and hepatic sarcoidosis. This review also addresses the management of alcohol use disorder in patients with chronic liver diseases as well as treatment considerations in patients who consume alcohol. With alcohol implicated in worsening outcomes across most liver conditions, abstinence is strongly recommended for patients with underlying liver diseases.

Alcohol use disorder (AUD) impacts many patients with alcohol-associated liver disease (ALD), affecting more than just the liver. ALD and AUD influence multiple organ systems, including neurologic, cardiovascular, gastrointestinal, hematologic, endocrine, and psychiatric. Recognizing these extrahepatic manifestations is essential for comprehensive patient care. Understanding how alcohol use affects these systems helps health care providers manage the full spectrum of health issues in patients with ALD. Addressing both liver-related and systemic effects of alcohol use ensures a more thorough and effective approach to treatment and patient outcomes.

This review article focuses on the management of alcohol use disorder (AUD) in patients with comorbid alcohol-associated liver disease (ALD). We highlight the importance of different screening tools for AUD in addition to the role of FDA and off-label medications for AUD and ALD treatment. For long-term recovery, we also speak to the importance of non-pharmacological interventions, including mutual aid organizations such as alcohols anonymous, peer recovery specialists, and emerging digital tools. Through a combination of these different tools, we can aid in patients in alcohol consumption reduction, abstinence improvement and ALD complication management.

Liver failure from alcohol can take on several forms, including decompensated alcohol-related cirrhosis (AC), acute-on-chronic liver failure (ACLF), and alcohol-related hepatitis (AH). While the definitions of decompensated AC and AH are well-established concepts in alcohol-related liver disease (ALD), ACLF is a contemporary and controversial concept of a severe form of acutely decompensated cirrhosis characterized by the existence of organ system failure(s) and a high risk of short-term mortality. While these terminologies have overlapping features, they are distinct and useful by capturing the varied clinical phenotypes within the spectrum of life-threatening ALD.

The psychosocial evaluation for liver transplant candidates with alcohol-associated liver disease (ALD) has evolved dramatically. The evaluation process has evolved from a stringent 6-month abstinence rule to robust, evidence-based assessment protocols incorporating disease severity scores, structured alcohol use assessments, biomarker testing, psychiatric evaluation, and validated risk prediction tools. These comprehensive evaluations aim to decrease rates of return to alcohol use and improve post-transplant patient and graft survival. We advocate for standardized, nonstigmatizing approaches to patient selection that balance responsible organ stewardship with recognition of ALD as a chronic, treatable condition.

Alcohol-associated liver disease has always been a significant health issue. During the coronavirus disease 2019 pandemic, there were higher rates of alcohol consumption, and these higher rates have persisted after pandemic. Given the significance of alcohol-associated liver disease, this article contextualizes disparities in alcohol-associated liver disease related to gender, socioeconomic status, and race/ethnicity. This article identifies a need for high-quality research on alcohol-associated liver disease, embedding of alcohol cessation metrics into hepatology quality measures, and colocation of social/psychosocial and addiction medicine resources into hepatology clinics as means of mitigating disparities and their impact on alcohol-associated liver disease and liver transplantation.

Alcohol-related liver disease (ALD) is a common cause of liver-related mortality and a leading indication for transplantation. On histopathology, bland steatosis is generally nonprogressive while steatohepatitis can lead to progressive fibrosis and eventually cirrhosis. Symptoms of ALD are minimal until the development of cirrhosis or alcohol-related hepatitis. Noninvasive testing can stage asymptomatic ALD and estimate prognosis. Alcohol abstinence remains the cornerstone of treatment of ALD. Treating comorbid liver diseases such as viral hepatitis or metabolic risk factors are also important to prevent ALD progression.

This narrative review explores post liver transplant (LT) management in patients with alcohol-related liver disease (ALD), emphasizing the challenges and strategies for preventing alcohol relapse. It discusses evolving practices like early liver transplantation, relapse risk factors, and evidence-based behavioral and pharmacologic interventions. With survival rates for ALD-LT recipients comparable to other LT populations, sustained abstinence and multidisciplinary care are critical for long-term success. The review also addresses monitoring protocols, psychosocial support, and management of comorbidities, offering clinicians a comprehensive framework to optimize patient outcomes and promote equitable, stigma-free care for individuals with ALD undergoing transplantation.

Alcohol-related liver injury is complex and remains poorly understood. Research to date has pinpointed the role of oxidative stress, hepatic inflammation, and derangements in lipid metabolism as drivers of disease pathogenesis. More recent research has identified alterations in the gut microbiome, epigenetics, G protein-coupled receptors, and microRNA's as possible drivers of disease pathogenesis and may serve as potential new treatment targets.

Alcohol-related hepatitis (AH) is the most acute and severe manifestation of alcohol-related liver disease. AH represents a spectrum of disease and portends poor prognosis with severe disease. Severe AH can have up to a 70% mortality at 6 months in medically refractory disease. Treatment options are limited and, thus, represent a critical unmet need. This review provides an overview of outcomes across the spectrum of disease severity in AH. We discuss current treatments available for AH, and how they apply to contemporary medical practice.

Severe alcohol-associated hepatitis (AH) is associated with high mortality and is rising in incidence but there are limited treatment options. Therapies being studied for AH include those targeting systemic cytokine-mediated inflammation, hepatic regeneration, reactive oxygen species, the microbiome, and genetics. Regenerative agents (such as granulocyte colony-stimulating factor, interleukin-22, and stem cell therapies) and therapies targeting the dysregulated microbiome hold the most promise and warrant larger trials. Manipulating the underlying genetics (eg, by gene editing of PNPLA3 or HSD17B13) is a lofty goal in personalized targeted therapy for AH but is many years from primetime.

Liver clinicians commonly encounter patients exhibiting hazardous patterns of alcohol use, including alcohol use disorder (AUD). Alcohol-associated liver disease (ALD) consists of severe psychosocial and biomedical hazards that necessitate clinicians' broad understanding of the natural history of this multifaceted chronic and relapsing condition. AUD involves myriad behavioral phenomena and data whose interpretation can be more subjective than biomedical data, thus requiring particular clarity in clinical terminology. ALD triggers strong emotional and moralistic reactions in clinicians, which can be the basis for stigma and other unproductive interactions that adversely affect clinical care and research.

Metabolic and alcohol/associated liver disease was introduced as a new term to describe those with steatotic liver disease who meet criteria for metabolic dysfunction-associated steatotic liver disease but exceed the allowable limits for alcohol within an upper limit of the equivalent of 50 to 60 g for females and males, respectively. Consumption beyond these limits would be characterized as alcohol-associated liver disease. Clinicians should focus on alcohol cessation counseling, metabolic risk factor management, as well as early referral to hepatology in those suspected to have significant fibrosis.

Imaging is essential in hepatocellular carcinoma (HCC) management, from screening to treatment assessment, but qualitative methods have limitations. Radiomics, a quantitative imaging approach, extracts high-dimensional features to enhance diagnostic, prognostic, and therapeutic decision-making. It shows promise in predicting treatment response and guiding personalized therapies. Integrating radiomics with artificial intelligence, particularly deep learning, could further improve predictive accuracy and clinical utility. Future efforts should focus on standardization, validation, and developing accessible tools to incorporate radiomics into routine therapeutic strategies, ultimately optimizing patient outcomes in HCC.

The disease burden of metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), represents an unmet need for pharmacotherapies to halt progression or reverse fibrosis. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are the first to be approved for chronic obesity management and diabetes to be examined in individuals with MASLD/MASH. Successful phase 2 and phase 3 randomized control trials have shown indirect improvements in liver fat, histology, and biomarkers. Over the last few years, newer agents with glucose-dependent insulinotropic peptide agonism and/or glucagon receptor agonism have shown considerable improvements in liver fat content and histology in phase 2 studies. Based on the mounting evidence, single, dual, and triple incretin receptor agonists are promising agents in the treatment of MASLD. In this narrative review, we evaluate weight loss pharmacotherapy for MASLD and then explore the potential for a "positive" disruption that these agents will bring to the existing management of MASLD in patients with obesity.

Artificial intelligence and machine learning are transforming hepatology by integrating clinical, laboratory, imaging, and wearable data for earlier diagnosis, risk prediction, and patient management. These technologies enable personalized care and noninvasive monitoring across metabolic dysfunction-associated steatotic liver disease, cirrhosis, hepatitis C, liver transplantation, and hepatocellular carcinoma. Ongoing advances in digital health and interpretability will enhance adoption and outcomes.

With recent advances in molecular medicine, there has been a transformation of the landscape of pediatric liver disease therapeutics. The advent of gene editing technologies, RNA therapeutics, and molecular chaperone therapies has led to precise targeting of liver pathology. This review aims to shed light on recent breakthroughs in liver-directed nucleic acid therapies such as small interfering RNA, mRNA editing, and CRISPR-based approaches, with a special focus on their application in alpha-1 antitrypsin deficiency, hepatitis B, cystic fibrosis-related liver disease, metabolic dysfunction-associated steatotic liver disease, Alagille syndrome, progressive familial intrahepatic cholestasis, and acute hepatic porphyria.

Primary sclerosing cholangitis (PSC) is a rare disease, autoimmune in nature, characterized by biliary strictures, chronic cholestasis, and progressive liver dysfunction. While its pathophysiology differs from primary biliary cholangitis (PBC), therapeutic targets still focus on bile acid regulation. PSC currently has no approved therapies, although several novel agents are under investigation. Cholestatic pruritus, a significant symptom in PSC and PBC, is now recognized as an approvable indication, with emerging therapies showing promise. This article highlights the investigational pipeline for PSC and cholestatic itch.