#302 - Confronting a metabolic epidemic: understanding liver health and how to prevent, diagnose, and manage liver disease | Julia Wattacheril, M.D., M.P.H.
Physician scientist Julia Wattacheril, M.D., M.P.H., discusses liver health, from alcohol impacts to liver function tests and stages of liver disease. She highlights the risks of liver disease in cancer and cardiovascular health, emphasizing strategies for diagnosis, treatment, and prevention.
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Quick takeaways
Understanding the significance of liver health in regulating blood glucose, detoxification, and managing lipoproteins.
Exploring the detrimental effects of ethanol metabolism on the liver, including inflammation, oxidative stress, and fat deposition.
Highlighting the challenges of quantifying alcohol intake and determining acceptable risk thresholds for alcohol-related harm.
Emphasizing the importance of comprehensive liver health assessments, including imaging studies and metabolic testing, in detecting early signs of liver injury.
Recognizing the impact of weight loss, exercise, nutrition, and specific medications like GLP1 agonists in improving metabolic and liver health.
Deep dives
Assessing Liver Disease and Translating Science
The focus of the Drive Podcast episode explores translational science in the context of liver health. The podcast delves into the basic physiology and four key functions of the liver, explaining the significant role of the liver in regulating blood glucose, detoxification, and managing lipoproteins. Special attention is given to the liver's metabolic functions, immune support, and synthetic protein production, highlighting its complexity and importance as a vital organ. The episode emphasizes the need to monitor for liver injury through various markers like liver function tests and underscores the liver's critical functions in maintaining overall health.
Understanding Alcohol-Related Liver Injury
The podcast episode discusses the mechanisms underlying alcohol-related liver injury. It delves into the metabolism of ethanol in the liver, highlighting the conversion of alcohol to acetaldehyde and the subsequent role of acetaldehyde in inducing liver damage. The episode emphasizes how acetaldehyde contributes to inflammation, oxidative stress, and fat deposition in the liver, leading to injury. The discussion also touches upon the challenges in metabolizing alcohol, genetic variations, and sex-based differences in alcohol metabolism. The complexity of alcohol metabolism and its impact on liver health are underscored, focusing on the toxicity of acetaldehyde and its role in liver inflammation and injury.
Evaluating Alcohol Consumption and Risk
In assessing alcohol consumption and associated risks, the podcast episode provides insights into determining acceptable levels of drinking and monitoring potential harm. It addresses the challenges of quantifying alcohol intake and determining risk thresholds, emphasizing the importance of understanding individual perceptions of alcohol-related risks. The episode discusses the significance of standard drink units, frequency of drinking, binge patterns, and the impact of social norms on alcohol consumption behaviors. Additionally, it highlights the role of liver specialists in quantifying alcohol use, measuring metabolites like phosphatidyl ethanol for assessing alcohol-related harm, and initiating discussions on alcohol consumption patterns and associated risks.
Quantifying Liver Injury and Health Assessments
The Drive Podcast episode explores the methods for quantifying liver injury and health assessments related to alcohol consumption. It delves into the utilization of tools like vibration-controlled transient elastography for evaluating hepatic steatosis and liver damage. The episode discusses the approaches to measuring liver health through markers like AST and ALT, emphasizing the value of bedside imaging techniques in detecting early signs of liver injury. It also sheds light on the significance of phosphatidyl ethanol testing in assessing alcohol-related harm over an extended period. The podcast underscores the importance of comprehensive liver health assessments, including metabolic functions and imaging studies, in evaluating alcohol-related liver disease and guiding interventions for better liver health.
Importance of Liver Enzyme Tests: AST and ALT
Liver enzyme tests like AST and ALT are essential for monitoring liver health. These enzymes help process substances in the liver under normal circumstances. Elevated levels of AST and ALT in the blood indicate liver cell stress or damage, possibly caused by factors like chronic liver disease or other conditions like alcohol consumption. Understanding the thresholds and changes in these enzymes over time can help detect liver issues early and guide further investigations.
Understanding Normal vs. Optimal Enzyme Levels
Defining what is 'normal' for liver enzymes AST and ALT has evolved over time, with thresholds varying for different diseases. Lab values now flag levels in the upper 40s or 50s, indicating a population-based shift in what is considered abnormal. Elevations in these enzymes suggest liver cell stress or damage, prompting a closer look into potential causes like alcohol consumption, viral hepatitis, or metabolic conditions.
Role of Lifestyle Changes in Managing Liver Health
Weight loss is a significant factor in improving metabolic and liver health, with exercise, sleep, and nutrition playing crucial roles. Tailoring exercise routines, dietary patterns, and considering coffee consumption, known for its potential benefits, may positively impact liver health. Additionally, addressing nutritional deficiencies and keeping a focus on micronutrients and macronutrients can enhance overall well-being.
Exploring Coffee and Fructose Concerns in Liver Health
Coffee has shown beneficial effects on various liver diseases due to its components, although the specific mechanisms are still being studied. When it comes to fructose consumption, high intake through processed forms like high fructose corn syrup can contribute to liver inflammation and injury, especially in cases of insulin resistance. Understanding the effects of fructose at isocaloric levels and its impact on liver health remains a topic of ongoing research.
Effective Treatment for Naphle D with GLP1 Agonists
GLP1 agonists like semaglutide and tersepetide have shown significant weight loss benefits and improved insulin sensitivity, making them potentially the most effective drugs for treating Naphle D and NASH. These drugs are particularly beneficial for known diabetics and individuals with BMI between 28 to 40 who have stage two estimations from non-invasive tests. While considering the use of these drugs, the emphasis is on published evidence and approved indications, especially when weight loss is a key factor but must be balanced with the potential for weight regain post-treatment and long-term disease progression.
Considering Oncology and Cardiovascular Risks in Early-Stage Naphle Disease
In the early stages of Naphle disease, the near-term risks of oncology and cardiovascular outcomes might outweigh the immediate hepatology risks. The focus on cardiovascular risk in clinical trials using major adverse cardiac events as an outcome underscores the close association between metabolic dysfunction and cardiovascular disease. The discussion also highlights the importance of empowering patients with information about potential risks and the need for thorough evaluation of clinical history to determine the most critical risks for an individual's long-term health.
Julia Wattacheril is a physician scientist and director of the Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) program at Columbia University Irving Medical Center. In this episode, Julia delves deep into the complex world of liver health, beginning with a foundational overview of liver physiology. She provides an in-depth look at how alcohol impacts liver function, breaking down the metabolism of ethanol and its detrimental effects. Julia then shifts the focus to understanding liver function tests and optimal enzyme levels, providing a detailed explanation of AST and ALT and elucidating why fluctuations in these levels may or may not be concerning. She provides a primer on the four major stages of liver disease, discussing risk and emphasizing the importance of early diagnosis. Julia highlights the role of liver disease in increasing the risk of cancer and cardiovascular disease and covers in detail the various strategies for diagnosing, treating, and preventing the progression of liver disease.
We discuss:
Julia’s training, the importance of liver health, and the challenges and innovations of hepatology [3:15];
The complex and crucial functionality of the liver, its four most essential functions, and more [8:45];
Liver injuries: historical and evolving understanding of causal factors, and the progression to liver diseases and cancer [13:15];
How the liver metabolizes nutrients and what happens in the presence of excess calories or alcohol [24:45];
Methods of diagnosing liver disease and how insights guide treatment and management strategies [33:30];
The poisonous nature of ethanol to the liver [40:30];
Varied responses to alcohol, damaging effects of alcohol beyond the liver, and the process of advising patients on their alcohol consumption [47:15];
Understanding liver enzymes AST and ALT—interpreting levels, lifestyle factors that affect them, and diagnostic approaches [58:30];
Interpreting liver function tests for fatty liver disease, and the challenges of diagnosing liver pathologies, particularly in children versus adults [1:13:15];
Comprehensive liver health assessments via imaging and various diagnostic tools to prevent overlooking potential liver pathologies [1:18:45];
Potential impact of recreational drugs, statins, and other medications on liver function test results [1:26:45];
Shifting nomenclature from NAFLD to MASLD to reflect accuracy in the underlying pathophysiology and understanding of liver diseases [1:30:30];
Pathophysiology of MASLD, the need for proactive screening, and the significance of liver fat percentage as an indicator of metabolic health [1:36:30];
The importance of screening for rare conditions alongside common metabolic diseases associated with fatty liver accumulation [1:42:45];
Practical strategies for managing MAFLD [1:45:30];
The impact of fructose consumption on liver health and the challenges of disentangling its effects from other factors like obesity and insulin resistance [1:52:45];
The potential of GLP-1 agonists for the treatment of MASLD [1:57:45];
How the four stages of liver disease have evolved [2:00:30];
Increased cancer and heart disease risk associated with early-stage MAFLD [2:05:15];
Emerging drugs and therapies for addressing fat accumulation and fibrosis related to MAFLD [2:12:15];
