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Questions and Answers
Which of the following are causes of chronic liver disease?
Which of the following are causes of chronic liver disease?
Chronic hepatitis is defined as chronic inflammation of the liver that persists for at least six months, or signs and symptoms of chronic liver disease in the presence of increased cytosolic enzymes.
Chronic hepatitis is defined as chronic inflammation of the liver that persists for at least six months, or signs and symptoms of chronic liver disease in the presence of increased cytosolic enzymes.
True
Clinical features of chronic hepatitis are highly variable.
Clinical features of chronic hepatitis are highly variable.
True
Most patients with chronic hepatitis are diagnosed because of an unexplained abnormality in aminotransferase activities or detection of positive results on a screening test for a cause of chronic hepatitis.
Most patients with chronic hepatitis are diagnosed because of an unexplained abnormality in aminotransferase activities or detection of positive results on a screening test for a cause of chronic hepatitis.
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Which of the following is a specific type of chronic hepatitis?
Which of the following is a specific type of chronic hepatitis?
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In the chronic replicative form, viral DNA is found in the cytoplasm of infected hepatocytes, and complete viral particles are produced and released into the circulation.
In the chronic replicative form, viral DNA is found in the cytoplasm of infected hepatocytes, and complete viral particles are produced and released into the circulation.
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Normally, hepatocytes express surface markers including HLA class 1 proteins.
Normally, hepatocytes express surface markers including HLA class 1 proteins.
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Primed lymphocytes then attack the infected hepatocytes.
Primed lymphocytes then attack the infected hepatocytes.
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What are the two key markers that assist in classifying types of chronic HBV infection?
What are the two key markers that assist in classifying types of chronic HBV infection?
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Chronic hepatitis B results when the immune response is incomplete, and the virus is not eliminated from infected cells.
Chronic hepatitis B results when the immune response is incomplete, and the virus is not eliminated from infected cells.
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20 to 30% of individuals with chronic hepatitis B will develop cirrhosis over a 20-year follow-up period; the risk is directly related to the amount of HBV DNA.
20 to 30% of individuals with chronic hepatitis B will develop cirrhosis over a 20-year follow-up period; the risk is directly related to the amount of HBV DNA.
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Once cirrhosis has developed, the annual risk of development of HCC is 1.5 to 5%.
Once cirrhosis has developed, the annual risk of development of HCC is 1.5 to 5%.
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Although the risk of HCC is lower in individuals with HBV infection who do not have cirrhosis, risk is directly related to viral load and rises at quantities above 2000 IU/mL.
Although the risk of HCC is lower in individuals with HBV infection who do not have cirrhosis, risk is directly related to viral load and rises at quantities above 2000 IU/mL.
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Even a person in the nonreplicating stage of infection has a 10-fold higher risk of HCC.
Even a person in the nonreplicating stage of infection has a 10-fold higher risk of HCC.
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Efficacy of treatment is measured by response of ALT and/or AST and HBV DNA.
Efficacy of treatment is measured by response of ALT and/or AST and HBV DNA.
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Goals of treatment include normalization of ALT and suppression of HBV DNA below the limits of detection of assays, ideally with detection limits of approximately 20 to 50 IU/mL.
Goals of treatment include normalization of ALT and suppression of HBV DNA below the limits of detection of assays, ideally with detection limits of approximately 20 to 50 IU/mL.
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Chronicity develops in approx. 80% of patients with HCV infection.
Chronicity develops in approx. 80% of patients with HCV infection.
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20 to 30% of patients with hepatitis C will progress to cirrhosis over 20 years.
20 to 30% of patients with hepatitis C will progress to cirrhosis over 20 years.
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The frequency of progression appears to be increased by age older than 40 years at the time of infection, male sex, alcohol abuse, and immunosuppression.
The frequency of progression appears to be increased by age older than 40 years at the time of infection, male sex, alcohol abuse, and immunosuppression.
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Cirrhosis risk is less than 5% after 20 years of infection in those infected during the first 20 to 30 years of life.
Cirrhosis risk is less than 5% after 20 years of infection in those infected during the first 20 to 30 years of life.
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In those who develop recurrent HCV after liver transplantation, the response rate is lower, and the rate of progression to cirrhosis is faster than in primary infection.
In those who develop recurrent HCV after liver transplantation, the response rate is lower, and the rate of progression to cirrhosis is faster than in primary infection.
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The likelihood of progression to HCC is between 1.5 and 5% per year in those with cirrhosis.
The likelihood of progression to HCC is between 1.5 and 5% per year in those with cirrhosis.
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Infection with HCV is characterized by fluctuating ALT activities over time.
Infection with HCV is characterized by fluctuating ALT activities over time.
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Only about one-third of those with chronic HCV have continually increased ALT.
Only about one-third of those with chronic HCV have continually increased ALT.
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Study Notes
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.
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Description
This quiz covers the causes and characteristics of chronic liver disease and chronic hepatitis. Key topics include toxins, viruses, metabolic disorders, and immune-mediated diseases affecting the liver. Test your understanding of the symptoms, diagnosis, and clinical presentation associated with these conditions.
