ASPARTATE AMINOTRANSFERASE (AST) Enzyme

ASPARTATE AMINOTRANSFERASE (AST)

• Enzyme present in tissues with high metabolic activity
• Released into circulation following cell injury or death
• AST levels rise within 12 hours and remain elevated for 5 days following severe cell damage
• Levels can be 10-100 times higher than normal in liver disease
• Elevated levels seen in acute and chronic hepatitis (ALT > AST) and active cirrhosis (AST > ALT)
• AST levels increase during the prodromal phase of hepatitis and are 20-30 times higher than normal in the icteric phase

ALPHA FETOPROTEIN

• Elevated levels associated with liver cancer
• Produced by the liver and used to monitor cancer treatment effectiveness
• Hepatocellular carcinoma biomarker reflecting tumor behavior and clinical prognosis

C REACTIVE PROTEIN

• Biomarker used in the context of hepatocellular carcinoma
• Marker of systemic inflammation

HEPATITIS A

• Formerly known as infectious hepatitis
• Transmitted through the fecal-oral route
• Risk factors include crowded, unsanitary conditions, and food and water contamination
• Caused by a small RNA-containing virus
• Virus replicated in the liver, excreted in bile, and shed in stool
• Incubation period is 2-4 weeks
• Individuals with the disease can be contagious for up to 2 weeks before the onset of symptoms
• Infection is more common than the actual disease
• By mid-adult life, about half of people in developed countries have evidence of infection (anti-HAV antibodies) but few recall being ill
• Disease does not cause a carrier state or chronic hepatitis

HEPATITIS B

• Transmitted through contact with infected blood, bodily fluids, or contaminated needles
• Maternal transmission can occur if the mother is infected during the third trimester
• Vaccine prevents transmission and development
• High risk of death from cirrhosis and liver cancer
• Transmission through blood, saliva, seminal, menstrual, and vaginal fluid
• Acute hepatitis B can cause acute liver failure and death
• Chronic hepatitis B can lead to cirrhosis and liver cancer
• Caused by a stranded DNA virus known as the Dane particle
• Transmitted through contact with infected blood, bodily fluid, or contaminated needles
• Maternal transmission can occur if the mother is infected during the last trimester

HEPATITIS PANEL HBV

• 3 antigens: 2 core (HBcAg and HBeAg), 1 surface antigen (HbsAg)
• 3 antibodies: anti-HBs, anti-HBc, anti-HBe
• IgM: antibodies in the acute state
• IgG: antibodies in the chronic state
• HBeAg appears soon after HbsAg, signifying viral replication
• HbsAg is a viral antigen that appears before the onset of symptoms, peaks during the acute disease, and then declines to undetectable levels in 3-6 months
• Anti-HBe is detectable shortly after the disappearance of HBeAg, signaling the onset of resolution of acute illness
• IgM anti-HBc is detectable shortly before the onset of symptoms, concurrent with an increase in serum transaminases
• Over time, IgM antibody is replaced by IgG anti-HBc
• IgG anti-HBs signals recovery from HBV infection, non-infectivity, and protection from future infection
• HBV DNA is a reliable marker of active HBV replication

4 PHASES OF HEPATITIS

• Incubation: period of initial exposure to the onset of symptoms
• Prodromal: begins 2 weeks after exposure and ends with the appearance of jaundice
• Icteric: begins 1-2 weeks after the prodromal phase and lasts for approximately 2-6 weeks
• Recovery phase (convalescent): begins with the resolution of jaundice, approximately 8 weeks after exposure

CHRONIC ACTIVE HEPATITIS

• Persists for more than 6 months and can lead to liver damage over time
• Constitutes a carrier state (patient harbors the virus, usually HBV, HCV, or HDV, without significant symptoms of liver disease)
• 70-80% of chronic cases are due to HCV
• Persistence of clinical manifestations and liver inflammation
• LFTs remain abnormal for longer than 6 months
• ALT depends on the level of disease activity, but is usually the first sign of infection
• HbsAg persists, and HBV DNA persists

CIRRHOSIS

• Irreversible inflammatory disease that disrupts liver function and structure
• Leading cause of death in the US, representing the end stage of chronic liver disease
• Normal liver architecture and function are disrupted with the development of diffuse fibrosis and nodular regeneration
• Obstruction can cause portal hypertension
• Blood shunting can lead to hypoxia, which can cause necrosis, atrophy, and failure

TYPES OF CIRRHOSIS

• Alcoholic cirrhosis (Laennec's cirrhosis)
• Primary biliary cirrhosis (cholangitis)
• Secondary biliary cirrhosis
• Post-necrotic cirrhosis (macronodular cirrhosis)

ESOPHAGEAL VARICES

• Varices are large, swollen veins
• Blood in the G.I. tract and spleen drain into the liver via the portal system
• In cirrhosis, the blood cannot flow easily into the liver
• Esophageal veins become overwhelmed with increased blood flow, leading to swelling and risk of bursting
• Portal hypertension: pressure rises in the portal system due to liver disease
• Pressure >6 is considered elevated, and pressure >10 is dangerous
• Varices seen most commonly in the esophagus, but also in the stomach, rectum, and small bowel
• Bleeding varices are life-threatening
• Causes of esophageal varices: portal hypertension, most commonly caused by cirrhosis due to excessive alcohol consumption or hepatitis