Chronic Hepatitis
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Basics
Description
- Chronic hepatitis is a continuous inflammation of the liver that can lead to cirrhosis.
- Features of chronic inflammation include raised transaminases for >6 months and histologic evidence of hepatocellular injury, cholestasis, or presence of inflammatory infiltration.
Epidemiology
Depends on the cause of the underlying disease
- Nonalcoholic steatohepatitis (NASH) is a leading cause of elevated alanine aminotransferase (ALT)/aspartate aminotransferase (AST).
- Hepatitis B: common in immigrant children from Asia and Eastern Europe
- Hepatitis C: common in those who had blood products before screening became available, history of IV drug use, tattoos, or in immigrant children with shared vaccination needles
- Hepatitis E: can cause chronic hepatitis in pregnant women
- Wilson disease presents mainly in older children (>2 years of age) and adolescents.
- Autoimmune hepatitis (AIH) is more common in females and patients >6 months of age. AIH may be associated with other autoimmune conditions such as primary sclerosing cholangitis (PSC), type I diabetes, inflammatory bowel disease, autoimmune thyroiditis, and celiac disease.
- Cystic fibrosis (CF) may present with cholestasis of the newborn; 5–10% of patients with CF develop advanced liver disease in childhood.
- α1-antitrypsin (AAT) deficiency phenotype (Pi) Pi*MM is wild type; Pi*ZZ or Pi*SZ cause liver disease.
Pathophysiology
Chronic hepatitis involves a continuous process of liver injury and regeneration.
- Pattern of liver injury and histopathology varies depending on the clinical diagnosis.
- The response to chronic liver injury is the same across most liver diseases: development of fibrosis.
- The liver is in a constant equilibrium between the production and breakdown of extracellular matrix (ECM) proteins, which includes collagen and others.
- Hepatitis causes increased cellular activation and transformation (e.g., activated stellate cells differentiate to myofibroblasts), which leads to the accumulation of ECM.
- Over time, as the connective tissue bands thicken they can extend from portal triad to portal triad (bridging fibrosis) or to central veins with eventual formation of nodules (cirrhosis).
Etiology
- Autoimmune liver disease: AIH or PSC
- Celiac disease associated with hepatitis
- Viral hepatitis
- Nonalcoholic fatty liver disease (NAFLD), or specifically NASH
- Congenital hepatic fibrosis
- Genetic disease
- AAT deficiency
- Alagille syndrome
- CF
- Progressive familial intrahepatic cholestasis (PFIC) syndromes
- Wilson disease
- Metabolic disease
- Mitochondrial disease
- Lysosomal acid lipase deficiency (LAL-D)
- Lysosomal storage disorders
- Peroxisomal disease
- Lipid storage disease
- Glycogen storage disease (GSD)
- Wilson disease and others
- Drug-induced liver injury (DILI)
- Parenteral nutrition–associated liver disease
- Chemotherapy: methotrexate, 6-mercaptopurine, thioguanine
- Isoniazid
- Valproate
- Liver disease associated with other chronic diseases
- Hypothyroidism, hyperthyroidism
- Growth hormone deficiency/panhypopituitarism
- Diabetes mellitus (uncontrolled hyperglycemia)
- Congestive hepatopathy (cardiac: right-sided heart failure or hypertension, such as post-Fontan procedure; pulmonary hypertension)
- Autosomal recessive polycystic kidney disease
- Langerhans cell histiocytosis
- Immunodeficiency
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Basics
Description
- Chronic hepatitis is a continuous inflammation of the liver that can lead to cirrhosis.
- Features of chronic inflammation include raised transaminases for >6 months and histologic evidence of hepatocellular injury, cholestasis, or presence of inflammatory infiltration.
Epidemiology
Depends on the cause of the underlying disease
- Nonalcoholic steatohepatitis (NASH) is a leading cause of elevated alanine aminotransferase (ALT)/aspartate aminotransferase (AST).
- Hepatitis B: common in immigrant children from Asia and Eastern Europe
- Hepatitis C: common in those who had blood products before screening became available, history of IV drug use, tattoos, or in immigrant children with shared vaccination needles
- Hepatitis E: can cause chronic hepatitis in pregnant women
- Wilson disease presents mainly in older children (>2 years of age) and adolescents.
- Autoimmune hepatitis (AIH) is more common in females and patients >6 months of age. AIH may be associated with other autoimmune conditions such as primary sclerosing cholangitis (PSC), type I diabetes, inflammatory bowel disease, autoimmune thyroiditis, and celiac disease.
- Cystic fibrosis (CF) may present with cholestasis of the newborn; 5–10% of patients with CF develop advanced liver disease in childhood.
- α1-antitrypsin (AAT) deficiency phenotype (Pi) Pi*MM is wild type; Pi*ZZ or Pi*SZ cause liver disease.
Pathophysiology
Chronic hepatitis involves a continuous process of liver injury and regeneration.
- Pattern of liver injury and histopathology varies depending on the clinical diagnosis.
- The response to chronic liver injury is the same across most liver diseases: development of fibrosis.
- The liver is in a constant equilibrium between the production and breakdown of extracellular matrix (ECM) proteins, which includes collagen and others.
- Hepatitis causes increased cellular activation and transformation (e.g., activated stellate cells differentiate to myofibroblasts), which leads to the accumulation of ECM.
- Over time, as the connective tissue bands thicken they can extend from portal triad to portal triad (bridging fibrosis) or to central veins with eventual formation of nodules (cirrhosis).
Etiology
- Autoimmune liver disease: AIH or PSC
- Celiac disease associated with hepatitis
- Viral hepatitis
- Nonalcoholic fatty liver disease (NAFLD), or specifically NASH
- Congenital hepatic fibrosis
- Genetic disease
- AAT deficiency
- Alagille syndrome
- CF
- Progressive familial intrahepatic cholestasis (PFIC) syndromes
- Wilson disease
- Metabolic disease
- Mitochondrial disease
- Lysosomal acid lipase deficiency (LAL-D)
- Lysosomal storage disorders
- Peroxisomal disease
- Lipid storage disease
- Glycogen storage disease (GSD)
- Wilson disease and others
- Drug-induced liver injury (DILI)
- Parenteral nutrition–associated liver disease
- Chemotherapy: methotrexate, 6-mercaptopurine, thioguanine
- Isoniazid
- Valproate
- Liver disease associated with other chronic diseases
- Hypothyroidism, hyperthyroidism
- Growth hormone deficiency/panhypopituitarism
- Diabetes mellitus (uncontrolled hyperglycemia)
- Congestive hepatopathy (cardiac: right-sided heart failure or hypertension, such as post-Fontan procedure; pulmonary hypertension)
- Autosomal recessive polycystic kidney disease
- Langerhans cell histiocytosis
- Immunodeficiency
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