06.1 Liver disease

Liver Disease Overview

• Liver disease encompasses various conditions, culminating in cirrhosis.
• Key contributors include metabolic-associated liver disease (MASLD), alcohol-related liver disease (ARLD), viral hepatitis, and autoimmune disorders.
• Terminology shifts (e.g., NAFLD to MASLD) reflect evolving understanding of the underlying pathophysiology, epidemiology, and clinical presentations.
• Diagnostic and management strategies are vital for clinical practice.

Learning Objectives

• Understand the pathophysiology and clinical presentation of MASLD, ARLD, viral hepatitis, cirrhosis, and autoimmune liver conditions.
• Define portosystemic anastomosis, its development, and common anatomical locations in liver disease.
• Describe how liver pathology leads to portal hypertension, including clinical signs and symptoms.
• Explain the relationship between liver pathology and hepatorenal syndrome.

Key Concepts and Definitions

• Cirrhosis: Chronic liver disease marked by inflammation, fibrosis, and nodular regeneration, causing structural impairment and diminished function. The final stage of many chronic liver diseases.
• NAFLD/MAFLD/MASLD:
  • NAFLD (Non-Alcoholic Fatty Liver Disease): Characterized by fat accumulation in hepatocytes (liver cells) without alcohol or other contributing factors (common since the 1980s).
  • MAFLD (Metabolic-Associated Fatty Liver Disease): Emphasizes the association with metabolic risk factors like obesity, type 2 diabetes, and hypertension. Alcohol consumption is not a primary concern. Introduced in 2020.
  • MASLD (Metabolic Associated Steatotic Liver Disease): A more recent (2024) definition incorporating both metabolic factors and alcohol consumption. The term "fatty liver" has been removed from this description to diminish stigma.
• ARLD (Alcohol-Related Liver Disease): Liver damage resulting from chronic alcohol consumption, encompassing a spectrum from hepatic steatosis (fatty storage) through alcoholic hepatitis (inflammation) to cirrhosis.
• Hepatitis: Inflammation of the liver, potentially caused by viruses (e.g., hepatitis B and C) or autoimmune disorders.
• Autoimmune Hepatitis: A rare, chronic inflammatory condition, more prevalent in women, often linked to other autoimmune diseases, with an unknown cause.

Clinical Applications

• A 50-year-old male with a BMI over 30, type 2 diabetes, and hypertension developed elevated liver enzymes. Non-invasive imaging showed over 5% liver fat (matching MASLD criteria). Lifestyle modifications were prescribed.
• Diagnostic approach focuses on liver fat quantification using MRI or ultrasound coupled with metabolic indicators such as triglycerides and blood glucose, and considers alcohol intake history and tools like the CAGE questionnaire (for ARLD cases).

Pathophysiology

• MASLD Pathway:
  • Steatosis: Excess fat accumulation in liver cells. Often reversible.
  • NASH (Non-Alcoholic Steatohepatitis): Inflammation and liver cell damage in the course of the disease.
  • Fibrosis: Build-up of fibrous tissue, altering liver architecture.
  • Cirrhosis: Irreversible scarring, nodular regeneration, and impaired function.
  • Approximately 30% of those with fatty livers progress to NASH, with 20–30% progressing from NASH to fibrosis and only about a small portion progressing to cirrhosis or HCC (Hepatocellular Carcinoma).
• Alcohol Metabolism in ARLD: Alcohol metabolizes into acetaldehyde triggering damaging effects.

Pharmacology

• Currently, no specific pharmacological treatments are available for MASLD; lifestyle changes are used primarily.
• Corticosteroids are a treatment option for acute alcoholic hepatitis.
• Research is focusing on developing treatments targeting pathways like acetaldehyde reduction and inflammation

Differential Diagnosis

• Distinguishing MASLD from ARLD relies primarily on patient history (alcohol use).
• Autoimmune hepatitis is identified through elevated IgG, autoantibodies (like ANCA and AMA), and related autoimmune symptoms.
• Primary Sclerosing Cholangitis (PSC) vs. Primary Biliary Cholangitis (PBC) are distinguished by their association with other conditions and specific autoantibodies.

Investigations

• Imaging (MRI, ultrasound) for liver fat quantification; MRI preferred for early stages, while ultrasound can provide additional details.
• Blood tests measure liver function (ALT, AST)), metabolic markers (triglycerides, glucose), and viral hepatitis antibodies.
• Consideration of autoimmune markers (ANCA, AMA), and questionnaires for alcohol consumption.

This quiz covers various liver diseases, including MASLD, ARLD, and cirrhosis. Explore the pathological mechanisms and clinical presentations associated with these conditions. Gain insights into diagnostic criteria and management strategies crucial for effective clinical practice.