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Approach to the Patient with Liver Disease¶

Chapter 347 | Part 10: Disorders of the Gastrointestinal System · Part 10 – Gastrointestinal Disorders · Chapter 347

Key Clinical Points¶

Liver disease patterns are classified as hepatocellular, cholestatic, or mixed.
Jaundice is the hallmark symptom; detectable at bilirubin >43 μmol/L (2.5 mg/dL).
Fatigue is the most common symptom, often intermittent and worse after activity.
CAGE questionnaire is recommended for assessing alcohol dependence.
Hepatic encephalopathy is defined by signs of hepatic encephalopathy in severe liver disease.
Trial-making test normal range is 15–30 seconds; prolonged time suggests encephalopathy.
Kayser-Fleischer rings are pathognomonic for Wilson disease (copper in Descemet's membrane).
Spider angiomata fill from center outward and occur on arms, face, and udder torso.
Blood transfusion before 1986 is a risk factor for Hepatitis B; before 1992 for Hepatitis C.
MRCP is superior to US/CT for detecting choledocholithiasis and congenital biliary abnormalities.
Liver biopsy is the criterion standard for grading activity and staging fibrosis.
Hepatopulmonary syndrome triad: hypoxemia, pulmonary arteriovenous shunting, platypnea-orthodeoxia.

DEFINITION & CLASSIFICATION¶

• Liver Anatomy: ◦ Weight: 1–1.5 kg (1.5–2.5% of lean body mass). ◦ Location: Right upper quadrant, under right lower rib cage against diaphragm. ◦ Blood Supply: Dual supply; ~20% oxygen-rich from hepatic artery, 80% nutrient-rich from portal vein. ◦ Cellular Composition: Majority are hepatocytes (two-thirds of mass); others include Kupffer cells (reticuloendothelial), stellate (Ito/fat-storing) cells, endothelial cells, bile ductular cells, and supporting structure cells. ◦ Organization: ◦ Lobules: Portal areas at periphery, central veins in center. ◦ Acini: Functional unit; blood enters from portal areas (zone 1) → flows through sinusoids to terminal hepatic veins (zone 3); intervening hepatocytes are zone 2.

• Liver Function: ◦ Synthesis: Serum proteins (albumin, carrier proteins, coagulation factors, hormones, growth factors). ◦ Production: Bile and carriers (bile acids, cholesterol, lecithin, phospholipids). ◦ Regulation: Nutrients (glucose, glycogen, lipids, cholesterol, amino acids). ◦ Metabolism: Conjugation of lipophilic compounds (bilirubin, anions, cations, drugs) for excretion.

• Microscopic Features: ◦ Sinusoids: Lined by unique endothelial cells with prominent fenestrae; allow plasma flow but not cellular elements. ◦ Space of Disse: Subendothelial space where plasma is in direct contact with hepatocytes. ◦ Hepatocyte Polarity: ◦ Basolateral side: Lines space of Disse, rich in microvilli; endocytotic and pinocytotic activity. ◦ Apical pole: Forms canalicular membranes for bile secretion. ◦ Kupffer Cells: Largest group of fixed macrophages in the body; located in sinusoidal vascular space. ◦ Stellate Cells: Located in space of Disse; produce collagen/matrix when activated.

• Classification of Liver Disease Patterns: ◦ Hepatocellular: Predominance of liver injury, inflammation, and necrosis (e.g., viral hepatitis, alcoholic liver disease). ◦ Cholestatic (Obstructive): Predominance of inhibition of bile flow (e.g., gallstone/malignant obstruction, primary biliary cholangitis, some drug-induced liver diseases). ◦ Mixed: Features of both hepatocellular and cholestatic injury (e.g., cholestatic forms of viral hepatitis, many drug-induced liver diseases).

• Table 347-1: Liver Diseases: ◦ Inherited hyperbilirubinemia: Gilbert syndrome; Crigler-Najjar syndrome (I & II); Dubin-Johnson syndrome; Rotor syndrome. ◦ Viral hepatitis: A, B, C, D, E; others (EBV, herpesvirus, cytomegalovirus, adenovirus). ◦ Cryptogenic hepatitis: Stone, stricture, cancer. ◦ Immune/Autoimmune: Primary biliary cholangitis, Autoimmune hepatitis, Sclerosing cholangitis, Overlap syndromes, Graft-versus-host disease, Allograft rejection. ◦ Genetic: α Antitrypsin deficiency, Hemochromatosis, Wilson disease, Benign recurrent intrahepatic cholestasis, Progressive familial intrahepatic cholestasis (I–III), others (galactosemia, tyrosinemia, cystic fibrosis, Niemann-Pick, Gaucher's). ◦ Alcohol-related: Acute fatty liver, Acute alcoholic hepatitis, Laënnec cirrhosis. ◦ Nonalcoholic fatty liver: Steatosis, Steatohepatitis, Acute fatty liver of pregnancy. ◦ Systemic involvement: Sarcoidosis, Amyloidosis, Glycogen storage diseases, Celiac disease, Tuberculosis, Mycobacterium avium-intracellulare. ◦ Cholestatic syndromes: Benign postoperative cholestasis, Jaundice of sepsis, TPN-induced jaundice, Cholestasis of pregnancy, Cholangitis/cholecystitis, Extrahepatic biliary obstruction (stone, stricture, cancer), Biliary atresia, Caroli disease, Cryptosporidiosis. ◦ Drug-induced: Hepatocellular (isoniazid, acetaminophen); Cholestatic (methyltestosterone); Mixed (sulfonamides, phenytoin); Steatosis (methotrexate, fialuridine); Vascular injury; Sinusoidal obstruction syndrome. ◦ Vascular injury: Budd-Chiari syndrome, Ischemic hepatitis, Passive congestion, Portal vein thrombosis, Nodular regenerative hyperplasia. ◦ Mass lesions: Hepatocellular carcinoma, Cholangiocarcinoma, Adenoma, Focal nodular hyperplasia, Metastatic tumors, Abscess, Cysts, Hemangioma.

EPIDEMIOLOGY¶

• General Risk Factors: ◦ Alcohol use, medication use (herbal, birth control, OTC), personal habits, sexual activity, travel, exposure to jaundiced persons, injection drug use, surgery, blood/blood product transfusion, occupation, needle-stick exposure, family history.

• Viral Hepatitis Risk Factors: ◦ Sexual Activity: ◦ Number of lifetime partners; for men, history of sex with men. ◦ Sexual exposure: Common for HBV and HDV; uncommon for HCV. ◦ Family history: Important for all types. ◦ Maternal-infant transmission: Occurs for HBV and HCV. ◦ Prevention (HBV): Passive/active immunization at birth; Antiviral therapy in 2nd/3rd trimester if HBV DNA >200,000 IU/mL. ◦ Prevention (HCV): No reliable means of prevention. ◦ Injection Drug Use: ◦ Significant for HBV, HCV, and HDV. ◦ Single most common risk factor for HCV. ◦ Blood Transfusion: ◦ Not a major risk for acute viral hepatitis due to screening. ◦ Risk for chronic HCV: Transfusions before 1992 (introduction of sensitive ELISA). ◦ Risk for HBV: Transfusions before 1986 (introduction of anti-HBc screening). ◦ Travel/Exposure: ◦ Hepatitis A: Travel to developing areas, exposure to jaundiced persons, daycare centers. ◦ Hepatitis E: Common in Asia/Africa; linked to fecally contaminated water. ◦ Non-travel cases in developed nations often due to swine/wild animal strains (genotypes 3 and 4) or raw pork/game. ◦ Chronic infection possible in immunocompromised individuals. ◦ Other Exposures: ◦ Tattooing/piercing: Rare risk for HBV, HCV, HDV. ◦ Shellfish: Risk for Hepatitis A.

• Alcohol-Related Liver Disease Risk Factors: ◦ Prevalence: 70% of US adults drink; only 5% have >2 drinks/day. ◦ Thresholds: ◦ Average drink: 11–15 g alcohol. ◦ Increased risk: >2 drinks (22–30 g) for women; >3 drinks (33–45 g) for men. ◦ Cirrhosis: Typically involves much higher intake and duration ≥10 years. ◦ Definitions: ◦ Abuse: Repetitive pattern with adverse effects on social, family, occupational, or health status. ◦ Dependence: Alcohol-seeking behavior despite adverse effects (more advanced form of alcoholism).

ETIOLOGY & PATHOPHYSIOLOGY¶

• Liver Anatomy and Physiology: ◦ Size/Shape: 1–1.5 kg; matches body shape. ◦ Location: Right upper quadrant, under right lower rib cage, against diaphragm. ◦ Blood Supply: ◦ Hepatic artery (20%): Oxygen-rich. ◦ Portal vein (80%): Nutrient-rich from stomach, intestines, pancreas, spleen. ◦ Organization: ◦ Lobules: Standard anatomical view; portal areas at periphery, central veins in center. ◦ Acini: Functional unit; blood flows from zone 1 (portal) → zone 2 → zone 3 (central). ◦ Bile Flow: Countercurrent flow from zone 3 to zone 1. ◦ Cellular Components: ◦ Hepatocytes: 2/3 of mass; perform synthesis, production, regulation, and metabolism. ◦ Kupffer Cells: Largest group of fixed macrophages in the body; located in sinusoidal space. ◦ Stellate Cells: Located in space of Disse; produce collagen/matrix when activated. ◦ Microcirculation: ◦ Sinusoids: Lined by fenestrated endothelial cells allowing plasma flow but not cellular elements. ◦ Space of Disse: Area where plasma is in direct contact with hepatocyte basolateral surface (rich in microvilli).

• Hepatocyte Functions: ◦ Synthesis: Serum proteins (albumin, carrier proteins, coagulation factors, hormones, growth factors). ◦ Production: Bile and carriers (bile acids, cholesterol, lecithin, phospholipids). ◦ Regulation: Nutrients (glucose, glycogen, lipids, cholesterol, amino acids). ◦ Metabolism: Conjugation of lipophilic compounds (bilirubin, anions, cations, drugs) for excretion.

CLINICAL FEATURES¶

• General Presentation: ◦ Symptoms: Jaundice, fatigue, itching, RUQ pain, nausea, poor appetite, abdominal distention, intestinal bleeding. ◦ Asymptomatic cases: Common; often found via routine labs or screening.

• Specific Symptoms: ◦ Fatigue: ◦ Most common/characteristic symptom. ◦ Description: Lethargy, weakness, listlessness, malaise, increased need for sleep, lack of stamina. ◦ Timing: "Afternoon" fatigue (worse after activity) rather than "morning" fatigue. ◦ Variability: Often intermittent and variable in severity. ◦ Nausea: ◦ More severe disease; may be triggered by food odors or fatty foods. ◦ Vomiting: ◦ Rare, not persistent/prominent. ◦ Poor appetite: ◦ Common in acute; rare in chronic unless cirrhosis is advanced. ◦ Diarrhea: ● Uncommon except with severe jaundice (lack of bile acids → steatorrhea). ◦ RUQ Pain ("Liver pain"): ● Due to stretching/irritation of Glisson's capsule. ● Common in gallbladder disease, liver abscess, and severe sinusoidal obstruction syndrome; occasionally acute hepatitis. ◦ Itching: ● Acute: Early in obstructive jaundice or drug-induced cholestasis; later in hepatocellular disease (acute hepatitis). ● Chronic: Typically in cholestatic forms; common once cirrhosis develops. ◦ Jaundice: ● Hallmark symptom; most reliable marker of severity. ● Observation: Patients often notice dark urine before scleral icterus. ● Threshold: Rarely detectable if bilirubin <43 μmol/L (2.5 mg/dL). ● Steatorrhea/Stool lightening: Seen with severe cholestasis. ● Jaundice without dark urine: Indicates indirect (unconjugated) hyperbilirubinemia (e.g., hemolytic anemia, Gilbert syndrome, Crigler-Najjar syndrome). ◦ Abdominal Distention: ● Ascites: Detected by shifting dullness; confirmed by US. ● Edema: May occur with or without ascites; factors include hypoalbuminemia, heart failure, etc.

• Physical Examination Findings: ◦ General Signs: Icterus, hepatomegaly, hepatic tenderness, splenomegaly, spider angiomata, palmar erythema, skin excoriations. ◦ Advanced Disease Signs: ● Muscle wasting, ascites, edema, dilated abdominal veins, hepatic fetor, asterixis, mental confusion, stupor, coma. ● Hyperestrogenemia (in males with cirrhosis): Gynecomastia, testicular atrophy, loss of male-pattern hair. ◦ Icterus: ● Best seen in natural light; skin may be yellow (fair skin) or mucous membranes below tongue (dark skin). ◦ Spider Angiomata & Palmar Erythema: ● Found in acute and chronic disease; prominent in cirrhosis. ● Distinction: Spider angiomata are tortuous arterioles filling from center outward. ● Location: Arms, face, upper torso. ◦ Hepatomegaly: ● Not highly reliable due to size/shape variability. ● Specificity: Typical of cirrhosis, sinusoidal obstruction syndrome, infiltrative disorders (amyloidosis), malignancy, alcoholic hepatitis. ● Key Finding: Hepatic tenderness is the most reliable finding in liver examination. ◦ Splenomegaly: ● Common in many conditions; subtle but significant in chronic liver disease suggesting cirrhosis. ◦ Advanced Signs & Syndromes: ● Umbilical hernia (from ascites), hydrothorax, caput medusa (collateral veins from umbilicus). ● Hyperdynamic circulation: Widened pulse pressure, increased cardiac output, reduced peripheral resistance. ● Hepatopulmonary Syndrome: ● Triad: Liver disease, hypoxemia, pulmonary arteriovenous shunting. ● Clinical Presentation: Platypnea and orthodeoxia (shortness of breath/oxygen desaturation upon standing). ● Screening: Pulse oximetry is reliable for detection. ◦ Skin Disorders: ● Hyperpigmentation: Chronic cholestatic diseases (PBC, sclerosing cholangitis). ● Xanthelasma & Tendon Xanthomata: Result of high serum lipids/cholesterol. ● Slate-gray pigmentation: Hemochromatosis with high iron. ● Mucocutaneous Vasculitis (palpable purpura): Chronic hepatitis C (also B). ◦ Specific Signs: ● Kayser-Fleischer rings: Pathognomonic for Wilson disease (copper in Descemet's membrane).

Specific Physical Signs¶

• Kayser-Fleichter Rings: Pathognomonic for Wilson disease. ◦ Location: Copper in Descemet's membrane.

DIFFERENTIAL DIAGNOSIS¶

• Etiologic Diagnosis: ◦ Based on history, physical exam, and laboratory tests. ◦ Radiologic exams are helpful or diagnostic in specific circumstances. ◦ Liver biopsy: Standard for grading (activity) and staging (fibrosis).

DIAGNOSTIC APPROACH¶

Initial Routine Testing:
Serum bilirubin, albumin, ALT, AST, AlkP.
γ-glutamyl transpeptidase (γGT) may be added to establish pattern (hepatocellular, cholestatic, or mixed).
Temporal Assessment:
Determine if disease is acute (<6 months) or chronic (≥6 months).
Pattern-Specific Workup (based on Figure 347-1):
Hepatitic Pattern (↑ ALT, ↑ AST):
ANA, SMA, IgG, Reticulocytes, Coagulopathy, Drug history.
Cholestatic Pattern (↑ AlkP, ↑ GGT):
ANA, P-ANCA, Fe saturation, Ultrasound, MRCP/ERC.
Imaging for Liver Fat (Table 347-4):
Ultrasound: No radiation; widely available; operator dependent; imprecise for mild steatosis.
Computed Tomography (CT): Rapid assessment; non-operator dependent; quantitative; requires specific protocols; not recommended for mild fat due to radiation/low sensitivity.
MRI: Direct assessment of liver fat; highly sensitive and specific; limited accessibility.
Noninvasive Fibrosis Assessment (Table 347-5):
APRI: (AST, platelet count, age, hyaluronic acid, MMP-3, TIMP-1).
Advanced Fibrosis: >1
Cirrhosis: >1.5 (1–2)
FIB-4: (Age, AST, ALT, platelet count, Haptoglobin, α-macroglobulin, apolipoprotein A1, γGT, total bilirubin).
Advanced Fibirs: >1.45
Cirrhosis: >3.25
FibroTest: (Specific test for fibrosis).
TE (Transient Elastography): Measures speed of shear wave.
Advanced Fibrosis: >7.3 kPa
Cirrhosis: >15 kPa (9–26.5 kPa)
Alternative Measurement: Speed of shear wave via acoustic radiation force; advanced fibrosis >1.3 m/s.
Specific Diagnostic Tests (Table 347-3):
Hepatitis A: Anti-HAV IgM.
Hepatitis C: Anti-HCV and HCV RNA.
Hepatitis E: Anti-HEV IgM and HEV RNA.
Primary Biliary Cholangitis: Mitochondrial antibody, elevated IgM levels, compatible histology.
Drug-induced Liver Disease: History of drug ingestion.
Nonalcoholic Steatohepatitis: Ultrasound or CT evidence of fatty liver and compatible histology.
Wilson Disease: Decreased serum ceruloplasmin, increased urinary copper, increased hepatic copper level.
Hepatocellular Cancer: Elevated α-fetoprotein (>500 ng/mL), ultrasound/CT image of mass.

Diagnostic Algorithm (Figure 347-1)¶

Initial Assessment: Suspected liver disease → Routine tests (Bilirubin, Albumin, ALT, AST, AlkP, γGT).
Classification:
Determine Pattern: Hepatocellular (↑ ALT/AST) vs. Cholestatic (↑ AlkP/GGT).
Determine Duration: Acute (<6 months) vs. Chronic (≥6 months).
Acute Pathway:
If Hepatitic → Workup: ANA, SMA, IgG, Reticulocytes, Coagulopathy, Drug history.
If Cholestatic → Workup: ANA, P-ANCA, Fe saturation, Ultrasound, MRCP/ERC.
Biopsy Decision: Preferred for diagnosis in the absence of other findings.
Chronic Pathway:
If Hepatitic → Workup: ANA, SMA, IgG, Reticulocytes, Coagulopathy, Drug history.
If Cholestatic → Workup: ANA, P-ANCA, Fe saturation, Ultrasound, MRCP/ERC.
Biopsy Decision: Often available for diagnosis as well as staging.

MANAGEMENT & TREATMENT¶

Hepatic Encephalopathy:
Clinical identification: Symptoms of hepatic encephalopathy in severe liver disease.
Assessment: Trial-making test (Normal: 15–30 seconds; prolonged indicates encephalopathy).

COMPLICATIONS & PROGNOSIS¶

• Skin Disorders and Changes: - Hyperpigmentation: Chronic cholestatic diseases (PBC, sclerosing cholangitis). - Xanthelasma/Tendon Xanthomata: High serum lipids/cholesterol. - Slate-gray pigmentation: Hemochromatosis. - Mucocutaneous vasculitis: Chronic hepatitis C (also B).

SPECIAL POPULATIONS¶

• Alcohol Dependence Assessment: - Tool: CAGE Questionnaire (Table 347-2). - C: Have you ever felt you ought to cut down on your drinking? - A: Have people annoyed you by criticizing your drinking? - G: Have you ever felt guilty or bad about your drinking? - E: Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover (eye-opener)? - Note: Any one answer is a strong indication of abuse or dependence.

KEY PEARLS & HIGH-YIELD POINTS¶

• Diagnostic Clues: - Jaundice: Bilirubin >43 μmol/L (2.5 mg/dL). - Hepatopulmonary Syndrome: Triad of liver disease, hypoxemia, and pulmonary arteriovenous shunting; characterized by platypnea and orthodeoxia. - Risk Factors: Blood transfusion before 1986 (HBV) or 1992 (HCV) are key historical markers.

• Exclusion Criteria: - Diagnosis of liver disease can often be made without symptoms if biochemical tests are abnormal.

Reference Tables¶

TABLE 347-1 Liver Diseases Inherited hyperbilirubinemia¶

Harrison's 22e, p.2628

Inherited hyperbilirubinemia
Gilbert syndrome
Crigler-Najjar syndrome, types I
and II
Dubin-Johnson syndrome
Rotor syndrome
Viral hepatitis
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis D
Hepatitis E
Others (Epstein-Barr virus
[mononucleosis] herpesvirus,
cytomegalovirus, adenovirus
hepatitis)
Cryptogenic hepatitis
Immune and autoimmune liver
diseases
Primary biliary cholangitis
Autoimmune hepatitis
Sclerosing cholangitis
Overlap syndromes
Graft-versus-host disease
Allograft rejection
Genetic liver diseases
α Antitrypsin deficiency
1
Hemochromatosis
Wilson disease
Benign recurrent intrahepatic
cholestasis
Progressive familial intrahepatic
cholestasis, types I–III
Others (galactosemia, tyrosinemia,
cystic fibrosis, Niemann-Pick-
disease, Gaucher’s disease)
Alcohol-related liver disease
Acute fatty liver
Acute alcoholic hepatitis
Laënnec cirrhosis
Nonalcoholic fatty livera
Steatosis
Steatohepatitis
Acute fatty liver of pregnancy

Liver involvement in systemic diseases
Sarcoidosis
Amyloidosis
Glycogen storage diseases
Celiac disease
Tuberculosis
Mycobacterium avium-intracellulare
infection
Cholestatic syndromes
Benign postoperative cholestasis
Jaundice of sepsis
Total parenteral nutrition–induced
jaundice
Cholestasis of pregnancy
Cholangitis and cholecystitis
Extrahepatic biliary obstruction
(stone, stricture, cancer)
Biliary atresia
Caroli disease
Cryptosporidiosis
Drug-induced liver disease
Hepatocellular patterns (isoniazid,
acetaminophen)
Cholestatic patterns
(methyltestosterone)
Mixed patterns (sulfonamides,
phenytoin)
Micro- and macrovesicular steatosis
(methotrexate, fialuridine)
Vascular injury
Sinusoidal obstruction syndrome
Budd-Chiari syndrome
Ischemic hepatitis
Passive congestion
Portal vein thrombosis
Nodular regenerative hyperplasia
Mass lesions
Hepatocellular carcinoma
Cholangiocarcinoma
Adenoma
Focal nodular hyperplasia
Metastatic tumors
Abscess
Cysts
Hemangioma

TABLE 347-2 CAGE Questions a ACRONYM C A G E a than one is a strong indication of abuse or dependence.¶

Harrison's 22e, p.2629

ACRONYM	QUESTION
C	Have you ever felt you ought to cut down on your drinking?
G	Have you ever felt guilty or bad about your drinking?

TABLE 347-3 Important Diagnostic Tests in Common Liver Diseases DISEASE Hepatitis A Hepatitis B¶

Harrison's 22e, p.2630

DISEASE	DIAGNOSTIC TEST
Hepatitis A	Anti-HAV IgM
Hepatitis C	Anti-HCV and HCV RNA
Hepatitis E	Anti-HEV IgM and HEV RNA
Primary biliary cholangitis	Mitochondrial antibody, elevated IgM levels, and compatible histology
Drug-induced liver disease	History of drug ingestion
Nonalcoholic steatohepatitisa	Ultrasound or CT evidence of fatty liver and compatible histology
Wilson disease	Decreased serum ceruloplasmin and increased urinary copper; increased hepatic copper level
Hepatocellular cancer	Elevated α-fetoprotein level (to >500 ng/mL); ultrasound or CT image of mass

TABLE 347-4 Diagnostic Tests to Assess Liver Fat¶

Harrison's 22e, p.2631

MAGING MODALITY	ADVANTAGES	DISADVANTAGES	CLINICAL UTILITY
Ultrasound	No radiation Widely available	Operator dependent Imprecise qualitative assessment of fat severity, particularly mild steatosis	Initial screening test for suspected liver fat
	No radiation Point-of-care assessment of liver fat Provides semiquantitative assessment of fat severity	Requires special software No reliable cutoff for diagnosis of liver fat Imprecise qualitative assessment of fat severity
Computed tomography	Rapid assessment Non–operator dependent Quantitative assessment of fat severity	Requires radiation Quantification of fat requires specific protocols Imprecise quantitative assessment of fat severity, particularly mild steatosis	Not recommended for clinical assessment of liver fat due to need for radiation exposure and low sensitivity for mild fat
	Direct assessment of liver fat Highly sensitive and specific	Relatively limited accessibility

TABLE 347-5 Selected Noninvasive Methods of Assessing Hepatic Fibrosis and Cirrhosis¶

Harrison's 22e, p.2632

METHOD	PARAMETERS	ADVANCED FIBROSIS	CIRRHOSIS
APRI	AST, platelet count	>1	>1.5 (1–2)
	Age, hyaluronic acid, MMP-3, TIMP-1	>7.7
FIB-4	Age, AST, ALT, platelet count	>1.45	>3.25
	Haptoglobin, α-macroglobulin, 2 apolipoprotein A1, γGT, total bilirubin	>0.45
TE	Measures speed of a shear wave generated by vibration through liver tissue	>7.3 kPa	>15 kPa (9–26.5 kPa)
	Measures speed of shear wave generated by acoustic radiation force through liver tissue	>1.3 m/s