Hepatitis and Liver Function Overview
Overview of Liver Functions
Hepatocytes:
Constitute approximately 70% of the liver's mass and are responsible for the vast majority of metabolic, synthetic, and detoxifying functions.
Key roles include protein synthesis (e.g., albumin, clotting factors), carbohydrate and lipid metabolism, bile production, and detoxification of endogenous and exogenous substances.
Kupffer Cells:
Specialized macrophages located in the liver sinusoids.
Primary function is phagocytosis, engulfing old or damaged red blood cells, bacteria, toxins, and other foreign particulate matter from portal blood.
Play a crucial role in the liver's immune surveillance and response.
Liver Functions and Storage
Storage:
Vitamins: The liver stores fat-soluble vitamins (A, D, E, K) and water-soluble vitamins, notably a significant reserve of B12 (cobalamin), which can last for several years.
Iron: Serves as the major storage site for iron, primarily in the form of ferritin and hemosiderin, essential for erythropoiesis and other metabolic processes.
Glycogen: Functions in glucose homeostasis by storing glucose as glycogen (glycogenesis) and releasing glucose into the bloodstream when needed (glycogenolysis) to maintain stable blood sugar levels, especially between meals.
Detoxification:
Converts a wide array of harmful substances (e.g., drugs, alcohol, metabolic waste products like ammonia) into less toxic, water-soluble compounds for excretion, primarily via urine or bile.
Involves two main phases: Phase I (oxidation, reduction, hydrolysis) and Phase II (conjugation with compounds like glucuronic acid or sulfate).
Fatty Acid Breakdown:
A primary function in lipid metabolism, involving beta-oxidation of fatty acids to produce acetyl-CoA, which enters the Krebs cycle for energy production or is used for ketone body synthesis when glucose is scarce.
Bilirubin Metabolism:
Critical for detoxifying bilirubin, a waste product from hemoglobin breakdown.
The liver conjugates indirect (unconjugated) bilirubin with glucuronic acid to form direct (conjugated) bilirubin, making it water-soluble for excretion in bile.
Dysfunction in this pathway is directly linked to jaundice and other liver health indicators.
Viral Hepatitis Overview
General Definition:
Hepatitis refers to inflammation of the liver, which can be triggered by a wide range of factors, including various viruses, alcohol consumption, autoimmune diseases, and certain medications.
Viral hepatitis specifically refers to liver inflammation caused by viral infections.
Primary vs. Secondary Hepatitis Viruses:
Primary: These are viruses whose primary target organ is the liver, including Hepatitis A, B, C, D, and E viruses.
Secondary: These are viruses that can cause hepatitis as part of a systemic infection, but the liver is not their main target. Examples include Epstein-Barr virus (EBV) (causing mononucleosis), Cytomegalovirus (CMV), Herpes Simplex Virus (HSV), HIV, HTLV1, and HTLV2.
Viral Hepatitis Symptoms:
Symptoms can range from asymptomatic to severe and life-threatening.
Common symptoms include jaundice (yellowing of skin and eyes due to bilirubin accumulation), dark urine (due to conjugated bilirubin in urine), fatigue, nausea, vomiting, abdominal pain (especially in the upper right quadrant), loss of appetite, and light-colored stools (due to lack of bile pigment).
Main Hepatitis Types
Hepatitis A
Transmission:
Transmitted primarily via the fecal-oral route, usually through ingestion of contaminated food or water.
Common sources include shellfish from contaminated waters, raw produce, or food handled by an infected person with poor hygiene.
Higher risk among restaurant and farm workers, travelers to endemic areas, and individuals living in conditions with poor sanitation.
Prevention:
Not a blood-borne virus; highly preventable through vaccination.
The vaccine offers long-lasting protection.
Good hand hygiene, especially after using the restroom and before eating or preparing food, is crucial.
Odds of transmission through blood transfusion are extremely low, approximately .
Hepatitis B
Transmission:
A blood-borne virus transmitted through percutaneous or permucosal exposure to infectious blood or body fluids (e.g., semen, vaginal secretions).
Common routes include needle sticks, sharing injection drug equipment, blood transfusions (less common now due to screening), unprotected sexual contact, and perinatal transmission (from infected mother to child during birth).
Vaccination:
Highly effective vaccine available.
Mandatory vaccination for newborns in the U.S. to prevent hepatitis B, with the first dose typically administered before hospital discharge to prevent perinatal transmission.
Also recommended for high-risk adults and healthcare workers.
Viral Markers:
Hepatitis B Surface Antigen (HBsAg): The first serologic marker detected during an acute infection, indicating active infection (acute or chronic).
Hepatitis B Surface Antibody (anti-HBs): Indicates immunity due to successful vaccination or recovery from a past infection. Its presence typically correlates with resolution of infection and protection from future infection.
Hepatitis B Core Antibody (anti-HBc): A marker of past or current infection. Anti-HBc IgM indicates acute infection, while anti-HBc total (IgG and IgM) indicates past or chronic infection.
Chronic Infection:
Defined by the persistence of HBsAg for more than six months.
Chronic carriers have prolonged presence of HBsAg and often test positive for anti-HBc. They are at increased risk for developing serious liver conditions like cirrhosis and hepatocellular carcinoma (HCC).
Anti-HBs positive indicates recovery or vaccination and immunity.
Hepatitis C
Characteristics:
A blood-borne RNA virus for which there is currently no vaccine.
Known for its high propensity to cause chronic infection; a majority of acute infections progress to chronicity, leading to a significant burden of liver disease.
Etiology:
Primarily spread through blood-to-blood contact.
Main routes include sharing contaminated needles or syringes among IV drug users, blood transfusions before 1992 (when screening became widespread), unprotected sex (less efficient but possible), and rarely, perinatal transmission.
Diagnosis:
Focus on early detection is crucial due to high rates of chronic infections, many individuals being unaware of their status until advanced liver disease develops.
Screening targets include individuals with risk factors, IV drug users, those who received transfusions before 1992, and all adults at least once in their lifetime.
Hepatitis D
Relationship to Hepatitis B