Chronic Liver Disease Overview

Chronic Liver Disease Causes

• Toxins (alcohol, drugs) are contributing factors
• Viruses (HBV, HCV) are causative agents
• Metabolic disorders (fatty liver disease, hemochromatosis, Wilson disease, AAT deficiency)
• Immune-mediated diseases (AIH, primary biliary cholangitis, primary sclerosing cholangitis)
• Liver infiltration
• Tumors (benign and malignant, primary and secondary)

Chronic Hepatitis

• Defined as persistent liver inflammation for at least 6 months, or signs/symptoms of chronic liver disease with elevated cytosolic enzymes.
• Characterized by ongoing hepatocyte inflammatory damage and scarring.
• Clinical presentation is variable; many patients are asymptomatic. Fatigue, lack of concentration, and weakness might also be present.
• Diagnosis is often via abnormal aminotransferase activities or positive screening results.
• Moderate aminotransferase increases (2–<5 times upper limit of normal (ULN)) are common; other tests are typically normal.
• Usually, alanine aminotransferase (ALT) is higher than aspartate aminotransferase (AST). AST/ALT > 1 suggests coexisting alcohol abuse or cirrhosis development.

Chronic HBV

• Incomplete immune response allows viral replication and reinfection of regenerating hepatocytes.
• Chronic HBV results in a continuing cycle of replication and reinfection of regenerating hepatocytes.

Chronic HBV Infection Patterns

• Occult: Normal aminotransferase (AST/ALT) levels, negative HBsAg, negative HBeAg, positive anti-HBc, and negative HBV DNA
• Immune control: Normal AST/ALT, positive HBsAg, negative HBeAg, positive anti-HBc, and negative HBV DNA
• Immune tolerant: Normal AST/ALT, positive HBsAg, positive HBeAg, positive anti-HBc, and positive HBV DNA
• Immune active: Elevated AST/ALT, positive HBsAg, positive HBeAg, positive anti-HBc, and positive HBV DNA
• HBeAg negative: Elevated AST/ALT, positive HBsAg, negative HBeAg, positive anti-HBc, and positive HBV DNA

Chronic HBV Prognosis

• 20-30% of individuals with chronic HBV develop cirrhosis over 20 years.
• The risk of cirrhosis is directly correlated with HBV DNA levels.
• Viral loads greater than 2000 IU/mL are associated with higher cirrhosis risk.
• Once cirrhosis develops, the annual risk of developing hepatocellular carcinoma (HCC) is 1.5–5%.

Chronic HCV

• Chronicity develops in ~80% of HCV infections.
• 20-30% progress to cirrhosis over 20 years.
• Risk factors for cirrhosis progression include age over 40 at infection, male sex, alcohol abuse, and immunosuppression.
• Cirrhosis risk is <5% after 20 years in those infected during ages 20-30.

Autoimmune Hepatitis (AIH)

• Rapidly progressive chronic hepatitis.
• Predominantly affects women aged 15-40, but all ages are susceptible.
• Associated with other autoimmune disorders (e.g., type 1 diabetes mellitus, thyroiditis, ulcerative colitis).
• HLA haplotypes (notably DR3 & DR4) associated.
• Specific liver and non-liver autoantibodies are detected.
• Diagnosis requires exclusion of other potential viral causes and histological features of inflammation and cell damage.

Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH)

• NAFLD: abnormal lipid accumulation in hepatocytes. Progresses from simple steatosis to necroinflammation and cirrhosis.
• NASH: NAFLD with hepatocyte inflammation, necrosis, and fibrosis.
• Risk factors include metabolic syndrome (impaired glucose tolerance, abdominal obesity, hypertension, HDL <40mg/dL (50mg/dL in females), triglycerides >150mg/dL)
• Diagnosis generally involves imaging and possibly liver biopsy.

Alcoholic Liver Disease

• Chronic and excessive alcohol consumption causes a range of liver conditions (steatosis, hepatitis, fibrosis/cirrhosis, HCC).
• Severity of damage correlates with duration and amount of alcohol consumption.
• Commonly seen in men > 40g/day and women > 10g/day.

Wilson Disease

• Autosomal recessive disorder of copper metabolism.
• Characterized by decreased biliary excretion and impaired incorporation of copper into ceruloplasmin.
• Copper accumulates in the liver, brain, and cornea.
• Typically presents as acute liver disease in children or with neurological symptoms in young adults.

Hemochromatosis

• Autosomal recessive disorder of iron metabolism.
• Characterized by excessive iron absorption and tissue deposition.
• Primarily affects organs like the liver, heart, pancreas, and joints.
• Often diagnosed through genetic testing and elevated iron related markers such as ferritin and transferrin saturation.

Hepatic Encephalopathy

• Metabolic disorder characterized by neuropsychiatric dysfunction.
• Often related to acute hepatic failure or chronic liver disease (cirrhosis).
• Manifests as disturbed consciousness, personality changes, abnormal reflexes etc.
• Commonly precipitated by GI bleed, drugs, high protein meals etc.

Ischemic Hepatitis

• Rapid, massive increase in liver aminotransferases due to reduced oxygen supply.
• Typically related to cardiac failure, sepsis, vascular disorders, or transplantation procedures.

Reye's syndrome

• Acute encephalopathy and liver injury following a viral infection, often with aspirin use.
• Characterized by rapid onset encephalopathy, abnormal liver function, and metabolic derangements (especially elevated ammonia levels).
• Especially in children and adolescents.

Acute Non-Viral Hepatitis

• Inflammation of the liver not caused by viruses.
• Triggered by chemical exposure, toxic substances, infections, supplements etc.

Liver Cirrhosis

• Advanced liver scarring resulting from persistent liver injury.
• Defined by the presence of abnormal nodular regeneration in a tissue biopsy sample and fibrous septae.
• Diagnosed via blood tests, liver biopsy and imaging techniques.
• Characterized by compensated (early) and decompensated (late) phases, often with complications like portal hypertension, ascites, jaundice etc.
• Prognosis is evaluated via MELD score.