Liver Disease Lecture Notes PDF

Liver disease Lecture Number 6.1 Status Done Type Lecture 6.1 Liver Disease Overview This lecture provides a comprehensive overview of various liver diseases, centering around cirrhosis as the end-stage manifestation for multiple liver conditions. Key pathways...

Liver disease Lecture Number 6.1 Status Done Type Lecture 6.1 Liver Disease Overview This lecture provides a comprehensive overview of various liver diseases, centering around cirrhosis as the end-stage manifestation for multiple liver conditions. Key pathways leading to cirrhosis include metabolic-associated liver disease (MASLD), alcohol-related liver disease (ARLD), viral hepatitis, and autoimmune liver conditions. Emphasis is placed on understanding shifts in terminology (e.g., NAFLD to MASLD), epidemiological data, underlying pathophysiological mechanisms, clinical presentations, and complications like portal hypertension and liver failure. Diagnostic and management strategies are explored to provide an integrated approach for clinical practice. Learning Objectives Objective 1: Describe the pathophysiology and clinical presentation of MASLD, ARLD, viral hepatitis, cirrhosis, and autoimmune liver conditions. Objective 2: Define portosystemic anastomosis, understand its development in liver disease, and identify common anatomical locations. Objective 3: Describe how liver pathology can lead to portal hypertension, including clinical signs and symptoms. Objective 4: Explain the relationship between liver pathology and hepatorenal syndrome. Key Concepts and Definitions Cirrhosis: Chronic liver disease characterized by ongoing inflammation, fibrosis, and nodular regeneration, leading to structural distortion and impaired liver function. Often the final stage for chronic liver conditions. NAFLD/MAFLD/MASLD: NAFLD (Non-Alcoholic Fatty Liver Disease): Coined in the 1980s, describes liver fat accumulation (>5% hepatocytes) without alcohol use or other secondary causes. MAFLD (Metabolic-Associated Fatty Liver Disease): Introduced in 2020, focuses on liver fat accumulation associated with metabolic risk factors (e.g., obesity, T2DM, hypertension) and disregards alcohol intake. Criteria include the presence of two metabolic factors (e.g., elevated triglycerides, central adiposity). MASLD (Metabolic-Associated Steatotic Liver Disease): Proposed in 2024, redefines the disease by incorporating both metabolic dysregulation and alcohol criteria, acknowledging the impact of low-to-moderate alcohol use. The term “fatty liver” was removed to reduce stigma. ARLD (Alcohol-Related Liver Disease): Liver damage resulting from chronic alcohol consumption. Spectrum includes hepatic steatosis, alcoholic hepatitis, and cirrhosis. Hepatitis: Inflammation of the liver, often caused by viruses (Hepatitis B, C) or autoimmune processes. Autoimmune Hepatitis: Rare, chronic liver inflammation of unknown cause; more common in females. Often associated with other autoimmune conditions (e.g., RA, SLE). Clinical Applications Case Study: A 50-year-old male with BMI >30, T2DM, and hypertension presents with elevated liver enzymes. Non- invasive imaging shows >5% liver fat, meeting MASLD criteria. Patient is advised on weight loss, Mediterranean diet, and moderate exercise as lifestyle modifications. Diagnostic Approach: Use MRI or ultrasound for liver fat quantification, followed by lab tests for metabolic indicators (e.g., triglycerides, blood glucose). In ARLD, conduct alcohol intake history and consider tools like the CAGE questionnaire.  Treatment Options: MASLD: Primarily lifestyle modifications—targeting weight loss, reducing sugar-sweetened beverages, and adopting a Mediterranean diet. ARLD: Emphasis on alcohol cessation, nutritional support, and corticosteroids for acute alcoholic hepatitis. Complications/Management: Portal Hypertension : Managed with beta-blockers to reduce pressure; TIPS (Transjugular Intrahepatic Portosystemic Shunt) for refractory cases. Varices: Oesophageal varices may require endoscopic interventions. Ascites: Managed with low-salt diets and diuretics. Pathophysiology MASLD Pathway: Steatosis: Excess liver fat (>5% hepatocytes), often reversible with lifestyle changes. NASH (Non-Alcoholic Steatohepatitis): Characterized by inflammation and cell damage; potential progression to fibrosis. Fibrosis: Formation of excess fibrous tissue, initiating architectural distortion. Cirrhosis: Irreversible end-stage with significant scarring, formation of regenerative nodules, and functional impairment. Hepatocellular Carcinoma (HCC): Small percentage may progress to HCC, though decompensated cirrhosis often precedes cancer. Note: Approximately 30% of those with steatosis progress to NASH, 20-30% from NASH to fibrosis, and only a small fraction to cirrhosis or HCC. Alcohol Metabolism in ARLD: Alcohol is metabolized to acetaldehyde, which promotes liver damage by increasing lipid accumulation, oxidative stress, and inflammation. Chronic exposure leads to hepatocyte injury, progressing through similar stages as MASLD. Pharmacology MASLD and ARLD: Currently, no pharmacological treatments specifically target MASLD; treatment is lifestyle-based. In ARLD, corticosteroids can be used in alcoholic hepatitis but carry infection risks. Research on potential pharmacotherapies is ongoing, focusing on pathways like acetaldehyde reduction and anti-inflammatory effects. Differential Diagnosis MASLD vs. ARLD: Distinction primarily relies on patient history (alcohol use). MASLD diagnosis requires metabolic risk factors (T2DM, central obesity) with liver fat >5%, regardless of moderate alcohol intake. Autoimmune Hepatitis: Identified by elevated IgG, autoantibodies (e.g., ANCA in PSC; AMA in PBC), and associated autoimmune symptoms. Primary Sclerosing Cholangitis (PSC) vs. Primary Biliary Cholangitis (PBC): PSC: Often affects men, associated with ulcerative colitis, with bile duct inflammation leading to fibrosis. PBC: More common in women, associated with conditions like rheumatoid arthritis, with bile duct destruction and presence of antimitochondrial antibodies (AMA) in 90% of cases. Investigations Imaging: MRI or ultrasound for liver fat quantification; MRI preferred for early-stage detection, while ultrasound  sensitivity increases with >20% fat. Blood Tests: Liver function tests (ALT, AST), metabolic markers (e.g., triglycerides, glucose), and viral serology for hepatitis. Autoimmune Markers: ANCA for PSC, AMA for PBC; raised IgG levels may indicate autoimmune hepatitis. Questionnaires: CAGE and AUDIT for alcohol consumption in ARLD assessments. Biopsy: Reserved for cases needing definitive diagnosis; typically avoided in MASLD unless further staging required. Key Diagrams and Visuals ALL ROADS LEAD TO CIRRHOSIS Summary and Key Takeaways Takeaway 1: MASLD has become the most prevalent liver disease globally, affecting around 30% of adults, especially those with metabolic conditions like T2DM. Takeaway 2: ARLD presents similarly to MASLD but has more rapid progression, especially with heavy alcohol use. Takeaway 3: Portal hypertension from cirrhosis can lead to life-threatening varices and ascites, requiring vigilant management. Further Reading/References "Non-Alcoholic Fatty Liver Disease and Cardiovascular Risk" - Targher et al., Journal of Hepatology, 2016. "Epidemiology and Mechanisms of ARLD" - Crabb et al., Hepatology, 2020. "Diagnostic Challenges and Advances in Liver Imaging for MASLD" - Rinella et al., Annals of Hepatology, 2023. Questions/Clarifications Question 1: What are the most effective ways to assess alcohol intake reliably in ARLD patients? Question 2: How does portal hypertension contribute to variceal formation in specific anatomical sites, such as the esophagus and rectum?