Liver Function

Liver General:

Functions & Resiliancy

• Large & Complex Organ

• Function:

  • Metabolism of carbs, lipids, proteins, bilirubin

  • Detox of harmful subs.

  • Storage of essential compounds

  • Clearance of waste products into bile or blood for extraction

• Resilient

  • Can regenerate with short term damage

  • regeneration is limited

Gross Liver Anatomy Overview

• Weight: 1.2–1.5 kg in healthy adult

• Location: Beneath & attached to diaphragm, protected by ribs

• Support: Held in place by ligaments (e.g., falciform ligament)

• Lobes: Right (larger), Left (smaller)

• Adjacent organs:

  • Gallbladder under right lobe

  • Stomach near left lobe

• Key anatomical relation: Lies directly below diaphragm, superior to most abdominal organs

Liver Vasculature & Lobular Structure

• Highly vascularized organ

• Two lobes:

  • Connected by falciform ligament

  • Right lobe is ~6× larger than left

• Dual blood supply:

  • Hepatic artery (25%) – oxygenated blood

  • Portal vein (75%) – nutrient-rich blood from GI tract

• ~1500 mL/min blood flow through liver

• Despite size difference, lobes are functionally equal

Bile Flow in the Hepatic Excretory System

• Begins in bile canaliculi (tiny channels between hepatocytes)

• Canaliculi → merge into right & left hepatic ducts

• Hepatic ducts → join to form the common hepatic duct

• Cystic duct from gallbladder joins → forms common bile duct

• Common bile duct empties into the duodenum

• Function: carries excretory products (e.g., bile) for digestion & waste removal

Hepatic Lobules & Liver Cell Types

• Liver divided into microscopic lobules

  • Hexagonal units with a central vein

  • Portal triads at each corner (portal vein, artery, bile duct)

  • Perform all excretory & metabolic functions

• Blood flows inward to central vein; bile flows outward to bile ducts

• Major cell types:

  • Hepatocytes (~80%) → metabolic workhorses

  • Kupffer cells → liver macrophages; phagocytose debris & toxins in sinusoids

Core Biochemical Roles of the Liver

• 4 essential functions:
  • Excretion/Secretion – bile, bilirubin, hormones
  • Storage – glycogen, vitamins (A, D, B12), iron
  • Metabolism – carbs, fats, proteins, drug processing
  • Detoxification – ammonia → urea, toxins, alcohol

• Vital for glucose homeostasis:
  • Liver maintains blood glucose via glycogenolysis and gluconeogenesis
  • If liver fails → severe hypoglycemia → coma/death

• Liver failure = fatal within 24 hours if glucose regulation ceases

Hepatic Excretion & Bile Formation

• Liver excretes endogenous & exogenous waste via bile or urine
  • Example: bilirubin from heme catabolism

• Only organ that can eliminate heme waste

• Bile composition:
  • Bile salts, bile pigments, cholesterol, and other extracted substances

• Liver produces ~3 L/day of bile, excretes ~1 L/day

• Bilirubin = primary bile pigment

Bilirubin Production Pathway

• RBC lifespan ≈ 120 days

• Aged RBCs are broken down, releasing hemoglobin

• Hemoglobin → heme, globin, and iron
  • Globin → amino acids (recycled)
  • Iron → bound to transferrin, sent to liver or marrow

• Heme → converted to bilirubin within 2–3 hrs

• Bilirubin → bound to albumin → transported to liver

Bilirubin Metabolism

• RBCs break down → heme → bilirubin

• Bilirubin binds albumin → travels to liver

• In liver:
  • Unconjugated bilirubin (water-insoluble)
  → becomes conjugated via UDP-glucuronyl transferase (water-soluble)

• Conjugated bilirubin → secreted into bile → intestines
  • Gut bacteria convert it to urobilinogen

• Fate of urobilinogen:
  • Majority → feces (gives stool brown color)
  • Some → reabsorbed → urine (1–4 mg/day)

Liver’s Role in Carbohydrate Metabolism

• One of liver’s most vital functions

• 3 ways liver processes glucose:
  • Uses it for own energy needs
  • Releases glucose to peripheral tissues
  • Stores it as glycogen

• Maintains blood glucose homeostasis via:
  • Glycogenesis – stores glucose as glycogen
  • Glycogenolysis – breaks down glycogen to glucose
  • Gluconeogenesis – makes glucose from non-carb precursors (e.g. amino acids)

Hepatic Lipid Metabolism Essentials

• Liver metabolizes lipids & lipoproteins under normal conditions

• Free fatty acids from diet → converted to acetyl-CoA

• Acetyl-CoA used to synthesize:
  • Triglycerides
  • Phospholipids
  • Cholesterol

• ~70% of daily lipid production comes from the liver, not the diet

Liver Functions in Protein Metabolism

• Almost all proteins are synthesized in the liver
  • Exception: immunoglobulins and adult hemoglobin

• Liver is essential for Hgb synthesis in infants

• Albumin = key plasma protein for oncotic pressure & transport

• Synthesizes:
  • Acute-phase reactants
  • Coagulation proteins
  • Amino acid pool storage

• Critical metabolic roles:
  • Transamination – transfers amino groups
  • Deamination – removes amino groups for energy use or urea cycle

Liver Detoxification & Drug Metabolism

• Filters waste from physiological processes (e.g. bilirubin, ammonia)

• Acts as gatekeeper: filters substances absorbed in GI tract before systemic release

• First-pass metabolism: all GI-absorbed substances pass through liver first
  → protects body from toxins/drugs entering circulation

• Two detox strategies:
  • Bind & inactivate compound
  • Chemically modify it for excretion

• Drug metabolism pathways:
  • Oxidation, reduction, hydrolysis, hydroxylation, carboxylation, demethylation

Liver Dysfunction in Disease States

• Jaundice – buildup of bilirubin (pre-, intra-, or post-hepatic causes)

• Cirrhosis – chronic liver damage → fibrosis, nodules, impaired function

• Tumors – hepatocellular carcinoma or metastatic lesions disrupt function

• Reye’s Syndrome – rare, acute liver failure (often post-viral in children)

• Drug & Alcohol Disorders – cause fatty liver, hepatitis, fibrosis, cirrhosis

Jaundice – Clinical Presentation & Thresholds

• Definition: Yellow discoloration of skin, sclera, mucous membranes

• Caused by retention of bilirubin in tissues

• Normal total bilirubin: 1.0–1.5 mg/dL

• Visible jaundice not seen until levels reach 3.0–5.0 mg/dL

Icterus & Jaundice Classification by Origin

Jaundice is classified by site of dysfunction:
• Prehepatic – excess RBC destruction → ↑ unconjugated bilirubin
• Hepatic – impaired conjugation or hepatocellular injury
• Posthepatic – bile duct obstruction → ↑ conjugated bilirubin buildup

Prehepatic (Unconjugated) Jaundice

• Caused by excess bilirubin production → overwhelms liver
  • Common in acute/chronic hemolytic anemias

• Characterized by unconjugated hyperbilirubinemia
  • Bound to albumin, not excreted in urine

• Bilirubin levels rarely exceed 5.0 mg/dL

Posthepatic (Obstructive) Jaundice

• Caused by biliary obstruction (e.g. gallstones, tumors)

• Conjugated bilirubin is formed but can’t be excreted into bile

• Bile flow blocked → no bilirubin enters intestines
  • Results in clay-colored stool due to absence of urobilinogen

Hepatic Jaundice – Intrinsic Liver Dysfunction

• Primary defect is in the liver itself

• Caused by:
  • Bilirubin metabolism or transport defects
  • Hepatocellular injury or destruction (e.g. hepatitis, toxins, cirrhosis)

• Leads to mixed elevation of conjugated & unconjugated bilirubin

Gilbert’s Syndrome

• Benign autosomal recessive disorder (~5% of U.S. population)

• No morbidity, mortality, or clinical consequences

• Intermittent unconjugated hyperbilirubinemia
  • Due to reduced conjugation activity (≈30% of normal function)

• Total bilirubin typically 1.5–3.0 mg/dL, rarely exceeds 4.5 mg/dL

Crigler-Najjar Syndrome

• Inherited disorder causing chronic, nonhemolytic unconjugated hyperbilirubinemia

• Caused by defective bilirubin conjugation enzyme

• Type 1: complete absence of enzyme → fatal without treatment

• Type 2: severe enzyme deficiency → milder but still dangerous

• Rare; may lead to kernicterus or death without proper managemen

Dubin-Johnson Syndrome

• Conjugated hyperbilirubinemia

• Rare autosomal recessive disorder, obstructive in nature

• Impaired excretion of conjugated bilirubin → buildup of delta bilirubin (bound to albumin)

• Dark-stained liver granules seen on biopsy

• Total bilirubin: 2–5 mg/dL

• No treatment needed, normal life expectancy

Rotor Syndrome

• Autosomal recessive liver disorder

• Rare & benign; no major clinical consequences

• Impaired hepatic uptake and clearance of bilirubin

• Labs: normal ALP and GGT → helps distinguish from biliary obstruction

Physiologic Jaundice

• NEONATAL HYPERBILIRUBINEMIA

• Seen in newborns, typically in the first week of life

• Caused by immature liver and deficiency of UDP-glucuronyl transferase (UDPGT)

• Unconjugated bilirubin builds up; premature infants at higher risk

• Can progress to kernicterus (bilirubin deposition in brain) → brain damage/death

• Dangerous levels: can exceed 20 mg/dL

• Treatment:
  • Phototherapy
  • Exchange transfusion
  • Pharmacologic therapy, IVIG, metalloporphyrins

Bilirubin Patterns in Jaundice Disorders

Condition	Total Bili	Conjugated	Unconjugated

Prehepatic

↑

↔

↑

Gilbert’s Syndrome

↑

↔

↑

Crigler-Najjar Syndrome

↑

↓

↑

Dubin-Johnson Syndrome

↑

↑

↔

Rotor Syndrome

↑

↑

↔

Jaundice of Newborn

↑

↔

↑

Posthepatic

↑

↑

↑

Cirrhosis

• Chronic liver disease → replacement of healthy tissue with scar tissue
  • Disrupts blood flow and normal liver function

• Often asymptomatic early; late signs: fatigue, jaundice, GI bleeding, ascites, pruritus

• Poor prognosis once advanced

• Most common cause: alcoholism
  • Treatment: abstinence

• Other causes: viral hepatitis (HBV, HCV, HDV), autoimmune hepatitis, NAFLD, toxins

• Treatment may include: interferons, corticosteroids

Liver Tumors

• Majority (90–95%) are metastatic from colon, lung, or breast

• Benign types: hepatocellular adenomas, hemangiomas

• Malignant types:
  • Hepatocellular carcinoma (HCC) – 90% of primary liver cancers
  • Bile duct carcinoma

• HCC risk factors: cirrhosis, HBV/HCV, heavy alcohol use, NAFLD, mycotoxins, smoking

• Malignant tumors have poor prognosis; survival measured in months

Reye’s Syndrome

• Pediatric disorder, often post-viral, with aspirin association

• Characterized by:
  • Noninflammatory encephalopathy
  • Fatty liver degeneration
  • Profuse vomiting, neurologic symptoms

• Labs:
  • Mild hyperbilirubinemia
  • ↑↑ ammonia, AST, ALT

• Untreated → rapid deterioration and possible death

Drug-Induced Liver Disease

• Accounts for 1/3–1/2 of acute liver failure cases in the U.S.

• Liver is a central site of drug metabolism → highly susceptible to injury

• Caused by many medications, with severity ranging from mild to fatal

• Most common mechanism:
  • Immune-mediated hepatocyte injury

Alcohol-Related Liver Disease

• Ethanol is the leading hepatotoxic drug

• 90% of alcohol is metabolized by the liver

• Low doses: mild, often unnoticed injury

• Chronic use → progression through 3 stages:
  • Alcoholic fatty liver
  • Alcoholic hepatitis
  • Alcoholic cirrhosis

• Severity and progression vary; exact toxic threshold is unknown

Fatty Liver Disease

• Typically very mild with few functional changes

• Slight increases in liver enzymes: AST, ALT, GGT

• Biopsy: fatty infiltration confirmed

• Common in middle-aged adults with:
  • Obesity, diabetes, moderate alcohol use

• Treatment: risk factor reduction, diet & exercise, diabetes control, limit alcohol

Alcoholic Hepatitis

• Symptoms: fever, ascites, muscle wasting, abnormal labs

• Labs:
  • Moderate elevation in AST, ALT, GGT, ALP
  • Total bilirubin often >5 mg/dL
  • Low serum albumin, ↑ prothrombin time
  • Rising creatinine = poor prognosis

• Severity and outcome depend on extent of liver damage

Alcoholic Cirrhosis

• Prognosis depends on complications (e.g. GI bleed, ascites)

• 5-year survival:
  • 60% with abstinence
  • 30% with continued drinking

• Symptoms: weight loss, weakness, hepatosplenomegaly, jaundice, ascites, edema

• Labs:
  • ↑ AST, ALT, GGT, ALP, bilirubin
  • ↓ albumin, prolonged prothrombin time

• Liver biopsy confirms diagnosis

Other Hepatotoxic Drugs

• Liver injury can range from mild to fatal failure or cirrhosis

• Risk drugs include:
  • Tranquilizers, some antibiotics
  • Antineoplastic agents, lipid-lowering drugs, anti-inflammatories

• Acetaminophen:
  • In large doses, causes fatal hepatic necrosis without rapid intervention

Bilirubin Testing History

• Based on the diazo reaction (Ehrlich, 1883); modern tests are modified versions

• Van den Bergh (1937) added accelerators to measure direct bilirubin

• Today:
  • Total and direct bilirubin measured
  • Indirect bilirubin is calculated

• Neonates: use bilirubinometry (light reflectance via skin)

• Bilirubin types:
  • Unconjugated (indirect), conjugated (direct), and delta (albumin-bound)

Bilirubin Fraction Determination (Diazo Method)

• Total bilirubin:
  • Bilirubin + diazotized sulfanilic acid + accelerator → azobilirubin

• Conjugated (direct) bilirubin:
  • Bilirubin + diazotized sulfanilic acid → azobilirubin

• Unconjugated (indirect) bilirubin:
  • Total bilirubin – conjugated bilirubin

Bilirubin Collection and Handling

• Use serum or plasma
  • Malloy-Evelyn method: prefers serum (avoids protein interference from alcohol)

• Fasting preferred: reduces lipemic interference

• Avoid hemolysis: hemoglobin inhibits diazo reaction

• Protect from light:
  • Exposure may cause 30–50% bilirubin loss per hour

Malloy-Evelyn Method

• Bilirubin reacts with diazotized sulfanilic acid

• Performed at pH 1.2

• Produces azobilirubin (red-purple, max absorbance at 560 nm)

• Methanol is the most common accelerator

• Less stable; light-sensitive reagent

endrassik-Grof Method

• Bilirubin reacts with diazo reagent in two aliquots
  • Diazo only → conjugated bilirubin
  • + caffeine-benzoate → total bilirubin

• Widely used (modified forms common)

• Advantages:
  • Not affected by pH or protein variation
  • High sensitivity, even at low bili
  • Minimal turbidity, constant serum blank
  • Tolerates hemoglobin up to 750 mg/dL

Adult Bilirubin Reference Ranges

• Direct (conjugated) bilirubin:
  • 0.0–0.2 mg/dL

• Indirect (unconjugated) bilirubin:
  • 0.2–0.8 mg/dL

• Total bilirubin:
  • 0.2–1.0 mg/dL

Urobilinogen

• Colorless end product of bilirubin metabolism

• Fate in body:

  • Some excreted in feces

  • Remainder reabsorbed → portal blood → liver

  • Small portion excreted by kidneys as urobilinogen

• In feces: oxidized by bacteria → brown pigment urobilin

• Clinical associations:

  • ↑ Urinary urobilinogen: hemolytic disease, hepatitis

  • ↓/Absent urobilinogen: complete biliary obstruction

Urobilinogen Testing

• Based on reaction w/ Ehrlich's reagent (p-dimethylaminobenzaldehyde)

• Forms red color

• Typically assessed in urinalysis, not chemistry

Liver Function Enzymes

• Used to assess liver injury and function

• Injury (e.g., cytolysis or necrosis) → enzymes released into circulation

• Enzymes help differentiate:

  • Hepatocellular (functional) vs. Obstructive (mechanical) damage

• Most useful LFTs:

  • ALT, AST (aminotransferases)

  • ALP, 5′-nucleotidase (phosphatases)

  • GGT

  • LD (lactate dehydrogenase)

Aminotransferases (ALT & AST)

• ALT = Liver-specific, rises more than AST, remains elevated 2–6 wks
  → ALT = “L” for Long & Liver

• AST = Found in heart, skeletal muscle, and liver

• Highest elevations seen in:

  • Acute viral hepatitis

  • Drug/toxin-induced necrosis

  • Hepatic ischemia

• Moderate elevations in less severe disease

• Present in multiple tissues → interpret cautiously

• Serial testing recommended—levels may drop in severe necrosis from depletion of hepatocellular stores

Alkaline Phosphatase (ALP)

• Widely distributed: highest in liver, bone, intestine, kidney, placenta

• Differentiates hepatobiliary disease vs osteogenic bone disease

• Very high ALP → extrahepatic biliary obstruction

• Slight to moderate elevation → hepatocellular disorders (e.g., hepatitis, cirrhosis)

Gamma-Glutamyl Transferase (GGT)

• Differentiates elevated ALP from skeletal vs hepatobiliary sources

• Highest levels in biliary obstruction

• Most sensitive hepatic enzyme indicator for liver disease

• Elevated by alcohol, enzyme-inducing drugs, and cholestasis

• Helpful when jaundice is absent to confirm hepatic neoplasms

Lactate Dehydrogenase (LD)

• Widely distributed throughout body

• Released with cell damage or destruction

• Acts as a nonspecific marker of injury

• Moderate ↑: acute viral hepatitis, cirrhosis

• Slight ↑: biliary tract disease

• High ↑: metastatic carcinoma of the liver

5′-Nucleotidase (5NT)

• Rarely ordered; performed at large reference labs

• No bone source → helpful with ALP to isolate liver origin

• ↑ in hepatobiliary disease

• More sensitive to metastatic liver disease

Tests of Hepatic Synthetic Ability

• Evaluates serum proteins to assess liver’s synthetic function

• ↓ Albumin → decreased protein synthesis

• ↓ Alpha-globulins in chronic liver disease

• ↑ Gamma-globulins in acute/chronic liver disease

  • IgG, IgM in chronic active hepatitis

  • IgM ↑ in primary biliary cirrhosis

  • IgA ↑ in alcoholic cirrhosis

• ↑ Prothrombin Time (PT) = poor prognosis, severe liver dysfunction

Tests Measuring Nitrogen Metabolism

• Liver clears ammonia from bloodstream by converting it to urea

• Ammonia levels reflect liver function

• ↑ Ammonia/toxins may cause hepatic coma
  (note: severity of symptoms doesn't always match ammonia level)

• Ammonia is unstable—must be kept on ice to prevent metabolism

Hepatitis

• Definition: Inflammatory condition of the liver

• Causes:

  • Non-infectious: Radiation, chemicals, autoimmune disease, toxins

  • Infectious:

    • Viral (most common): HAV, HBV, HCV, HDV, HEV

    • Bacterial, parasitic

• Acute symptoms: Jaundice, dark urine, fatigue, nausea, vomiting, abdominal pain

• Chronic hepatitis:

  • Transaminase elevation >6 months

  • Common with HBV and HCV

HAV - Key Features

• Aka infectious hepatitis or short incubation

• Most common form worldwide (~1.5 million cases annually)

• Caused by non-enveloped RNA virus (Picornavirus)

• Transmission: fecal-oral route (via food, water)

• Excreted in bile and shed in feces

HAV - Symptoms & Prognosis

• Symptoms: fever, malaise, anorexia, nausea, abdominal discomfort, dark urine, jaundice

• Self-limiting: resolves in ~3 weeks

• Liver failure is rare

• No chronic infection or carrier state

HAV - Vaccination

• Vaccines available: offer long-term immunity

• Recommended for children and travelers to endemic areas

HAV - Diagnosis: Serology

• IgM anti-HAV:

  • Appears early; detects acute infection

  • Detectable at/just before symptoms

  • Disappears by 3–6 months

• IgG anti-HAV:

  • Appears after IgM

  • Persists for life = immunity

  • IgM–, IgG+ = past infection

HAV - Diagnosis: Other Methods

• Fecal antigen detection during acute phase

• Disappears after liver enzymes peak

• RT-PCR:

  • More sensitive than immunoassay

  • Useful for asymptomatic cases

  • Works with various sample types

HCV – Clinical Features & Transmission

• RNA virus, parenterally transmitted (blood products, IV drug use).

• Leading cause of liver transplants in the U.S.

• ~2.5% of world infected; ~2.4 million U.S. cases.

• Often asymptomatic acutely, but 80% become chronic.

• High risk of progression to cirrhosis, carcinoma.

• No vaccine available; treatment via antiviral meds.HCV

HCV – Testing & Monitoring

• Initial screen: anti-HCV antibody (EIA).

• If positive → confirm with HCV RNA (PCR).

• Anti-HCV not detectable in early infection window.

• Chronic cases monitored by RNA viral load.

• Vaccine unlikely due to viral variability.

Hepatitis D

• Small, defective RNA virus

• Requires HBsAg from HBV to replicate → can't infect alone

• Must also have HBV to get HDV infection

  • Coinfection: HDV + HBV at same time

  • Superinfection: HDV after chronic HBV → more severe

• ~5% of global HBV carriers have HDV

• Serologic patterns (coinfection vs. superinfection):

  • Coinfection: HBsAg+, Anti-HBc IgM+, HDVAg+, Anti-HDV ±

  • Superinfection: HBsAg+, Anti-HBc IgM–, HDVAg+, Anti-HDV+

Hepatitis E

• Fecal-oral transmission; waterborne outbreaks

• Incubation: 21–42 days

• Virus detected in feces ~7 days post-infection

• Zoonotic potential: pigs, cows, sheep are reservoirs

• Clinically resembles HAV

• Diagnosed by anti-HEV IgM

• No vaccine available

Other Forms of Hepatitis

• Hepatitis F: Enteric agent; transmissible to primates

• GB virus C (Hep G): Flaviviridae; infects humans, no disease

• No diagnostic tests available

• Other viral causes:

  • Cytomegalovirus (CMV)

  • Epstein-Barr virus (EBV)

  • SARS-CoV-2

Global Burden and Symptoms of HBV

• AKA serum hepatitis or "long incubation" hepatitis

• Can be acute or chronic

• Most ubiquitous hepatitis virus

  • ~2 billion infected globally

  • 1.5 million new cases annually

• U.S. stats:

  • ~12 million infected

  • Peak incidence: ages 25–45

• Common symptoms:

  • Jaundice, fever, dark urine, pale stool

  • Fatigue, nausea, abdominal pain (right abdominal)

  • Anorexia, joint pain, headache, hives

Transmission Routes and Environmental Stability

• Survives >7 days on surfaces

• Present in all body fluids, including:

  • Blood, feces, urine, saliva, semen, tears, breast milk

• Transmission modes:

  • Parenteral (e.g., needle sharing, medical exposure)

  • Perinatal (mother-to-child at birth)

  • Sexual contact

Populations at High Risk for HBV Infection

• High-risk behaviors:

  • Unprotected sex

  • Needle sharing

• Perinatal transmission:

  • Infants born to HBsAg+ mothers

• Geographic risk:

  • Immigrants from endemic areas

• Household & sexual contacts of infected persons

• Blood transfusions:

  • Risk is rare, but still possible

HBV Structure and Antigens

• HBV is a DNA virus

• Liver = primary site of viral replication

• Infection process:

  • Antigen core synthesized in hepatocyte nuclei

  • Moves to cytoplasm

  • Surrounded by a protein coat

• Key antigens:

  • HBcAg: core antigen, found inside virus

  • HBsAg: surface antigen, located on outer envelope

  • HBeAg: secreted antigen, linked to viral replication and infectivity

HBsAg – Hepatitis B Surface Antigen

• Detected before symptoms appear

• Used to screen all donated blood units

• Indicates presence of HBV, but is not itself infectious

• Chronic carriers of HBsAg = potentially infectious

  • Cannot rule out intact virus

• Antibody to HBsAg develops after complete viral clearance

HBsAg – Detection and Diagnostic Window

• First serologic marker to appear after HBV infection

  • Detected in 3–5 weeks

• Average time to detection:

  • 30 days post-exposure (range: 6–60 days)

• Nucleic acid tests can detect HBV DNA

  • Positive 10–20 days before HBsAg

• May be transiently positive 10–20 days post-vaccination

Anti-HBs – Hepatitis B Surface Antibody

• Indicates past infection or successful vaccination

• Appears after HBsAg clearance

• Confers immunity to future HBV infection

• Common in general population due to prior exposure or immunization

• Used to assess:

  • Recovery from natural infection

  • Response to vaccination

Anti-HBs – Interpretation of Results

• Positive result:

  • Indicates recovery from acute or chronic HBV

  • Reflects acquired immunity

• Negative result:

  • Suggests no recovery from infection

  • May indicate inadequate immune response

HBcAg – Hepatitis B Core Antigen

• Not detectable in blood—no test available for patients or donors

• Intracellular only: found in hepatocyte nuclei during acute infection

• Anti-HBc (core antibody) develops before Anti-HBs

Anti-HBc, Total – Interpretation and Utility

• Detects past or chronic HBV infection

• Appears during “window period” when HBsAg and Anti-HBs are negative

• Useful in distinguishing recent vs chronic infection (w/ IgM status)

Interpretation summary:

• Anti-HBc Total (+) → past or chronic infection

• Anti-HBc IgM (+) → acute or recent infection

• Anti-HBc IgM (–) → past or chronic infection

• Anti-HBc Total (–) → no evidence of recent, past, or chronic infection

• Anti-HBc Total (inconclusive) → possible interfering substances

• HBsAg (+) with Anti-HBc Total (+) → chronic infection

Anti-HBc IgM – Marker of Acute HBV Infection

• Specific for acute HBV infection

• May persist at low levels in chronic HBV

• Can be reactivated (test positive) during exacerbation of chronic HBV

Hepatitis B Envelope Antigen

• Found in serum during acute or chronic HBV

• Closely linked to the viral core

• Correlates with:

  • Viral replication

  • Number of infectious particles

  • Infectivity of serum

• Anti-HBe formation → low infectivity

• HBeAg + HBsAg → poor prognosis, predicts chronic infection and severe disease course

Bridges structure with prognosis

Anti-HBe – Hepatitis B Envelope Antibody

• Appears as HBeAg declines during recovery from acute infection

• Remains detectable for several years

• In chronic infection:

  • Low levels signal low infectivity and reduced transmission risk

Contextual note: Complements HBeAg—marks transition from high to low infectivity

HBV Serology Timeline – Recovery Pattern

• HBsAg appears first, peaks during acute illness

• HBeAg follows, indicating infectivity

• Anti-HBc IgM signals recent infection

• Anti-HBe emerges as HBeAg declines

• Anti-HBs appears after clearance of HBsAg → immunity

• Window period: Anti-HBc may be the only positive marker

Contextual note: Diagram shows acute → resolved infection with sequential seroconversion.

Just know general trends

HBV Serology Timeline – Chronic Infection Patterns

• HBsAg persists >6 months → chronic HBV

• HBeAg may persist (poor prognosis) or decline with Anti-HBe formation (better outcome)

• No Anti-HBs formed in chronic infection

• Anti-HBc (total) stays positive regardless of chronicity

Just know general trends

Chronic Hepatitis B – Outcomes and Risk Factors

• 90% of patients recover within 6 months (develop Anti-HBs)

• 10% develop chronic hepatitis:

  • Risk highest with perinatal infection (90%)

  • 20–30% risk with infection during childhood

• Among chronically infected:

  • 25% infected since childhood and

  • 15% infected as adults will die prematurely from cirrhosis or liver cancer

Phases of Chronic Hepatitis B Infection

• Immune Tolerance:

  • Virus present, but immune system unresponsive

• Immune Clearance:

  • Active immune response, HBeAg+, liver inflammation

• Inactive Carrier State:

  • HBsAg+, but low/absent viral replication

• Reactivation:

  • Return of viral replication, often with HBeAg reappearance

  • Indicates chronic active hepatitis

Chronic HBV – Active vs Inactive Serologic Profiles

Marker	Active Replicating	Non-Replicating
HBsAg	+	+
Anti-HBs	–	–
Anti-HBc	+	+
HBeAg	+	–
Anti-HBe	–	+

---

Contextual note: Use this profile to distinguish chronic active infection (high infectivity) from inactive carrier state—ties directly to the 4-phase model and timeline diagrams.

NEED TO KNOW THIS CHART FOR EXAM

Categorize by the Active/non replicating, maybe switch format of chart

HBV – Treatment and Prevention

• Ongoing medical monitoring is essential

• Antiviral therapy can suppress HBV replication

• Vaccination is the most effective tool for HBV prevention

Contextual note: Vaccination leads to Anti-HBs production—mimicking recovery from infection without exposure to the virus.

HBV Vaccination Guidelines and Efficacy

• National childhood immunization program began in 2005

  • ↓ 98% in cases among <13 y/o

  • ↓ 97% in cases among 12–19 y/o

• Vaccination recommended for all at-risk adults, including:

  • Healthcare workers

• Non-responders may receive a second vaccine series

Contextual note: Vaccination is the only route to Anti-HBs without prior infection—essential for prevention, especially in high-risk groups.

Hepatitis Viruses – Key Differences

Virus	Genome	Incubation	Transmission	Vaccine	Chronic?	Serology?
A	RNA	2–6 wk	Fecal–oral	Yes	No	Yes
B	DNA	8–26 wk	Parenteral, sexual	Yes	Yes	Yes
C	RNA	2–15 wk	Parenteral, sexual	No	Yes	Yes
D	RNA	2–8 wk	Parenteral, sexual	No	Yes	Yes
E	RNA	3–6 wk	Fecal–oral	No	Yes	Yes

Contextual note: This table is useful for differentiating hepatitis types on exams, especially when comparing transmission, chronicity, and vaccine availability.

Want me to move on to the two timeline-based flashcards now?