This article reviews surveillance for the detection of early stage hepatocellular carcinoma, covering the rationale for surveillance, optimal selection of persons needing surveillance, methods and frequency of screening,...This article reviews surveillance for the detection of early stage hepatocellular carcinoma, covering the rationale for surveillance, optimal selection of persons needing surveillance, methods and frequency of screening, strategies for addressing barriers to surveillance, and trends for future improvement in surveillance leading to more effective cancer control and improved patient outcomes. The importance of integrating liver cancer surveillance as a core component of national public health programs is emphasized. The impact of emerging technologies for identifying persons at risk, stratifying individual risk to improve the cost-effectiveness of surveillance programs, and improving the performance, accessibility, and convenience of surveillance are discussed.
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, and 85% to 90% of cases of HCC occur in patients with underlying liver disease. This makes it a complex illness to treat, because disease...Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, and 85% to 90% of cases of HCC occur in patients with underlying liver disease. This makes it a complex illness to treat, because disease burden occurs not only from the cancer, but also potential decompensation of the underlying liver disease. Palliative care is multifaceted care that addresses physical, spiritual, and psychosocial needs of patients and can provide support for their caregivers. It can help in advance care planning and hospice support. Early integration of palliative care can improve patient qualify of life and patient/caregiver satisfaction.
Management of cirrhosis sequelae is critical in providing the most options for patients with hepatocellular carcinoma (HCC). Compensated liver disease is the ideal state for HCC patients who may require resection, locore...Management of cirrhosis sequelae is critical in providing the most options for patients with hepatocellular carcinoma (HCC). Compensated liver disease is the ideal state for HCC patients who may require resection, locoregional therapies, or liver transplantation. Portal hypertension complications, suboptimal nutrition, and frailty are common barriers to various HCC treatments. For patients with advanced HCC, systemic therapies are altering the approach to multifocal, unresectable HCC, but similar barriers exist related to managing cirrhosis complications. Frequently, managing the underlying liver disease etiology is a key component to enabling HCC treatment.
Hepatocellular carcinoma (HCC) presentation reflects a complex interaction between cancer stage, severity of liver disease, and overall functional status. This article provides clinical vignettes that illustrate these co...Hepatocellular carcinoma (HCC) presentation reflects a complex interaction between cancer stage, severity of liver disease, and overall functional status. This article provides clinical vignettes that illustrate these complex interactions and how a multidisciplinary approach can result in rational, evidence-based plans of care that factor in the local standard of care as well as patient preference. The vignettes range from a patient with early stage HCC and good liver function to a patient with metastatic disease. The full spectrum of treatments that can be applied ranging from curative surgery and transplantation to locoregional therapy and systemic therapy are shown.
Systemic therapy for hepatocellular carcinoma has evolved from sorafenib to now include immune checkpoint blockade, either atezolizumab/bevacizumab or durvalumab/tremelimumab, and soon to include camrelizumab/rivoceranib...Systemic therapy for hepatocellular carcinoma has evolved from sorafenib to now include immune checkpoint blockade, either atezolizumab/bevacizumab or durvalumab/tremelimumab, and soon to include camrelizumab/rivoceranib and nivolumab/ipilimumab. Second-line therapy remains predominantly either a multikinase inhibitor or ramucirumab. Areas of development include testing immune checkpoint-based regimens in the adjuvant setting after surgery, ablation, or transarterial embolization. Also of interest are studies for patients with Child-Pugh B liver function and adding new checkpoint molecules to the current standard platforms.
The epidemiology of hepatocellular carcinoma (HCC) has shifted significantly in the last 2 decades with non-viral etiologies such as metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver d...The epidemiology of hepatocellular carcinoma (HCC) has shifted significantly in the last 2 decades with non-viral etiologies such as metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease on the rise. Key factors include the global obesity epidemic and the resurgence of alcohol use disorder, both of which were exacerbated by the coronavirus disease 2019 pandemic. While these non-viral etiologies of HCC are becoming the leading cause in developed countries, the potential impact of immigration patterns on Hepatitis B virus epidemiology cannot be ignored. The risk of HCC remains significant in individuals with cirrhosis and viral hepatitis after curative treatments.
Liver is the most common organ affected by alcohol misuse. The spectrum of alcohol-associated liver disease (ALD) ranges from simple steatosis to cirrhosis and its complications. The unique clinical phenotype of alcohol-...Liver is the most common organ affected by alcohol misuse. The spectrum of alcohol-associated liver disease (ALD) ranges from simple steatosis to cirrhosis and its complications. The unique clinical phenotype of alcohol-associated hepatitis has a risk for high short-term mortality. Several gaps exist with respect to epidemiology, noninvasive testing, prognostication, and treatment of ALD. Most studies focus on short-term survival as the ideal endpoint and ignore other aspects of alcohol-use disorder and ALD. In this review, the authors discuss the existing knowledge gaps, enumerate ongoing clinical trials, and highlight the research priorities and future landscape of clinical trials.
Artificial intelligence (AI) has the potential to aid in the diagnosis and management of alcohol-associated liver disease (ALD). Machine learning algorithms can analyze medical data, such as patient records and imaging r...Artificial intelligence (AI) has the potential to aid in the diagnosis and management of alcohol-associated liver disease (ALD). Machine learning algorithms can analyze medical data, such as patient records and imaging results, to identify patterns and predict disease progression. Newer advances such as large language models (LLMs) can enhance early detection and personalized treatment strategies for individuals with chronic diseases such as ALD. However, it is essential to integrate LLMs and other AI tools responsibly, considering ethical concerns in health care applications and ensuring an evidence base for real-world applications of the existing knowledge.
Alcohol-associated liver disease is a well-validated indication for liver transplantation and recent data have refined the patterns of alcohol consumption and their impact on the pre-LT and post-LT periods. The selection...Alcohol-associated liver disease is a well-validated indication for liver transplantation and recent data have refined the patterns of alcohol consumption and their impact on the pre-LT and post-LT periods. The selection process is a multidisciplinary approach that integrates liver and addiction parameters. The present review analyzes the drivers of outcome and alcohol relapse and focuses on the changing paradigm in terms of access to the waiting list.
Alcohol-associated liver disease (ALD) is the most common cause of liver disease and an indication for liver transplantation. Identification of ALD at an earlier stage and treatment of concomitant alcohol use disorder (A...Alcohol-associated liver disease (ALD) is the most common cause of liver disease and an indication for liver transplantation. Identification of ALD at an earlier stage and treatment of concomitant alcohol use disorder (AUD) could potentially prevent or delay the progression to advanced stages of ALD like alcohol-associated cirrhosis and alcohol-associated hepatitis. However, screening for alcohol use is often not performed and treatment of AUD is rarely administered in ALD patients, due to several barriers at the level of patients, clinicians, and administrative levels.
Clin Liver Dis
· 2024 Nov · PMID 39362721
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The cornerstone in managing alcohol-associated liver disease is the treatment of alcohol use disorder (AUD). Several barriers prevent the implementation of adequate treatment and integrated care models. There are patient...The cornerstone in managing alcohol-associated liver disease is the treatment of alcohol use disorder (AUD). Several barriers prevent the implementation of adequate treatment and integrated care models. There are patient-level barriers, including the lack of self-awareness of AUD and being ashamed of AUD. There are clinician-level barriers, including lack of training and discomfort in managing patients with AUD. There are system-level barriers, including challenges related to insurance-based health care systems, and the general reluctance to invest in AUD by organizations focused on for-profit milestones. Therefore, it is imperative to develop multidisciplinary hepatology/addiction integrated care approaches.
Clin Liver Dis
· 2024 Nov · PMID 39362720
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The prevalence of alcohol use disorder (AUD) has significantly increased over the last decade, leading to an increase in alcohol-associated liver disease (ALD) rates worldwide. Despite this prominence, AUD in ALD remains...The prevalence of alcohol use disorder (AUD) has significantly increased over the last decade, leading to an increase in alcohol-associated liver disease (ALD) rates worldwide. Despite this prominence, AUD in ALD remains undertreated and carries significant implications in the progression to end-stage ALD and increased mortality. In efforts to bridge this gap, interprofessional and integrated AUD treatment is necessary for patients with ALD to ensure early detection and an appropriately targeted level of care. Although pharmacotherapy, psychotherapy, and psychosocial interventions independently play a role in treating AUD, a combination of these evidence-based modalities often results in lasting change.
Several treatments have shown efficacy in preliminary alcohol-associated hepatitis trials. Interleukin-22 improved Model of End-stage Liver Disease score and aminotransferases in a phase II trial. The endogenous choleste...Several treatments have shown efficacy in preliminary alcohol-associated hepatitis trials. Interleukin-22 improved Model of End-stage Liver Disease score and aminotransferases in a phase II trial. The endogenous cholesterol derivative, larsucosterol, improved outcomes in a multi-center United States or European phase II trial. The antioxidants N-acetylcysteine and metadoxine improved survival in large trials. Trials from India report improved survival with granulocyte-colony stimulating factor, as well as improved outcome among patients receiving fecal microbiota transfer. Translational studies suggest that phage treatment of cytolytic Enterococcus faecalis may reduce liver injury.
Clin Liver Dis
· 2024 Nov · PMID 39362718
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Patients with alcohol-associated liver disease (ALD) consume large amounts of empty calories and are at risk for malnutrition. Malnutrition can present with micro- or macro-nutrient deficiencies. The standard-of-care dru...Patients with alcohol-associated liver disease (ALD) consume large amounts of empty calories and are at risk for malnutrition. Malnutrition can present with micro- or macro-nutrient deficiencies. The standard-of-care drug treatment for severe alcohol-associated hepatitis (AH) is corticosteroids. While still in the standard treatment there are limitations in efficacy and certain patients do not respond to treatment (Lille score ≥.45). This article will focus on important concepts related to nutrition and ALD and on recent findings on predicting corticosteroid response and prognosis for AH patients.
Alcohol-associated liver disease (ALD) remains a significant public health concern, accounting for at least half of cirrhosis cases in Europe. Historically, liver biopsy has been considered the gold standard method for b...Alcohol-associated liver disease (ALD) remains a significant public health concern, accounting for at least half of cirrhosis cases in Europe. Historically, liver biopsy has been considered the gold standard method for both diagnosing and staging ALD. However, in the past 3 decades, there has been a growing interest in developing noninvasive biomarkers for identifying high-risk patients prone to develop liver-related complications, including elastography methods or blood-based biomarkers. This review aims to summarize currently available noninvasive testing methods that are clinically available for assessing patients with ALD, including notably steatosis and fibrosis.
Witkiewitz K, Fernandez AC, Green EW
… +1 more, Mellinger JL
Clin Liver Dis
· 2024 Nov · PMID 39362716
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Harmful alcohol use and alcohol use disorder (AUD) are common worldwide, and rates of alcohol-associated liver disease (ALD) are also increasing. AUD is a disease that is treatable and can be diagnosed and managed, and r...Harmful alcohol use and alcohol use disorder (AUD) are common worldwide, and rates of alcohol-associated liver disease (ALD) are also increasing. AUD is a disease that is treatable and can be diagnosed and managed, and recovery from AUD through abstinence or reductions in drinking is possible. Management of AUD among individuals with ALD is increasingly being addressed via integrated medical and psychosocial treatment teams that can support reductions in drinking and prevent progression of liver disease. Early diagnosis of AUD and ALD can improve lives and reduce mortality.
Alcohol use, while commonly associated with liver damage, also has significant neurologic implications, which often mimic hepatic encephalopathy and complicate diagnosis and management. Alcohol mediates its acute central...Alcohol use, while commonly associated with liver damage, also has significant neurologic implications, which often mimic hepatic encephalopathy and complicate diagnosis and management. Alcohol mediates its acute central nervous system effects by altering neurotransmitter balance, notably between gamma-aminobutyric acid and glutamate. Its chronic neurotoxicity, compounded by thiamine deficiency, results in chronic neurologic complications. Clinically, alcohol-related neurologic disorders present a spectrum from acute intoxication and withdrawal to chronic conditions like Korsakoff syndrome, dementia, cerebellar degeneration, and peripheral neuropathy. This review underscores differentiating these conditions from hepatic encephalopathy and highlights the importance of history-taking and physical examination in clinical practice.
Clin Liver Dis
· 2024 Nov · PMID 39362714
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Alcohol-associated liver disease (ALD) poses a significant global public health challenge, with high patient mortality rates and economic burden. The gut microbiome plays an important role in the onset and progression of...Alcohol-associated liver disease (ALD) poses a significant global public health challenge, with high patient mortality rates and economic burden. The gut microbiome plays an important role in the onset and progression of alcohol-associated liver disease. Excessive alcohol consumption disrupts the intestinal barrier, facilitating the entry of harmful microbes and their products into the liver, exacerbating liver damage. Dysbiosis, marked by imbalance in gut bacteria, correlates with ALD severity. Promising microbiota-centered therapies include probiotics, phages, and fecal microbiota transplantation. Clinical trials demonstrate the potential of these interventions to improve liver function and patient outcomes, offering a new frontier in ALD treatment.
Clin Liver Dis
· 2024 Nov · PMID 39362713
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The pathogenesis of alcohol-associated liver disease (ALD) is complex and multifactorial. Several intracellular, intrahepatic, and extrahepatic factors influence development of early fatty liver injury leading to inflamm...The pathogenesis of alcohol-associated liver disease (ALD) is complex and multifactorial. Several intracellular, intrahepatic, and extrahepatic factors influence development of early fatty liver injury leading to inflammation and fibrosis. Alcohol metabolism, cellular stress, and gut-derived factors contribute to hepatocyte and immune cell injury leading to cytokine and chemokine production. The pathogenesis of alcohol-associated hepatitis (AH), an advanced form of acute-on-chronic liver failure due to excessive chronic intake in patients with underlying liver disease, is not well understood. While pathogenic mechanisms in early ALD are studied, the pathogenesis of AH requires further investigation to help design effective drugs for patients.