APPROACH TO THE PATIENT WITH LIVER DISEASE
Source: Harrison 20th Edition
INTRODUCTION
▪ A diagnosis of liver disease usually can be made
accurately by careful elicitation of the patient’s history,
physical examination and few laboratory tests
▪ Radiologic examinations - are helpful or, indeed,
diagnostic
▪ Liver biopsy - is considered the criterion standard in
evaluation of liver disease, but is now needed less for
diagnosis than for grading (activity) and staging
(fibrosis) of disease
▪ Non-invasive means of assessing fibrosis stage
have become increasingly helpful and may allow for
avoidance of biopsy in a proportion of patients.
LIVER STRUCTURE AND FUNCTION
LIVER
o Largest organ of the body
o Weight: 1–1.5 kg ( representing 1.5–2.5% of the lean
body mass)
oSize and Shape: vary and generally match the
general body shape—long and lean or squat and
square
o Location: right upper quadrant of the abdomen under
the right lower rib cage against the diaphragm and
projects for a variable extent into the left upper
quadrant
o Held in place by: ligamentous attachments to the
diaphragm, peritoneum, great vessels, and upper
gastrointestinal organs
o Dual blood supply: ~20% of the blood flow is oxygen-
rich blood from the hepatic artery
: 80% is nutrient-rich blood from the portal vein
arising from the stomach, intestines, pancreas,
and spleen
LIVER CELLS
1. Hepatocytes – majority of cells in the liver ( constitute
two-thirds of the organ’s mass)
o have distinct polarity
= basolateral side of the hepatocyte lines the space of
Disse and is richly lined with microvilli; it exhibits
endocytotic and pinocytotic activity, with passive and
active uptake of nutrients, proteins, and other
molecules
= apical pole of the hepatocyte forms the canalicular
membranes through which bile components are
secreted. The canaliculi of hepatocytes form a fine
network, which fuses into the bile ductular elements
near the portal areas
o Functions:
o synthesis of most essential serum proteins (albumin,
carrier proteins, coagulation factors, many hormonal
and growth factors)
o the production of bile and its carriers (bile acids,
cholesterol, lecithin, phospholipids)
o the regulation of nutrients (glucose, glycogen, lipids,
cholesterol, amino acids)
o the metabolism and conjugation of lipophilic
compounds (bilirubin, anions, cations, drugs) for
excretion in the bile or urine
o most commonly used liver “function” tests are
measurements of serum bilirubin, serum albumin, and
prothrombin time
o serum bilirubin level - measure of hepatic
conjugation and excretion
o serum albumin level and prothrombin time -
measures of protein synthesis
*Abnormalities of bilirubin, albumin, and prothrombin
time are typical of hepatic dysfunction
*Frank liver failure is incompatible with life, and the
functions of the liver are too complex and diverse to
be subserved by a mechanical pump; a dialysis
membrane; or a concoction of infused hormones,
proteins, and growth factors
2. Kupffer cells (members of the reticuloendothelial
system)
o usually lie within the sinusoidal vascular space
and represent the largest group of fixed
macrophages in the body
3. Stellate (Ito or fat-storing) cells
o located in the space of Disse but are not usually
prominent unless activated, when they produce
collagen and matrix
4. Red Blood Cells
o stay in the sinusoidal space as blood flows
through the lobules, but white blood cells can
migrate through or around endothelial cells into
the space of Disse and from there to portal
areas, where they can return to the circulation
through lymphatics
5. Endothelial and Blood Vessel Cells, Bile Ductular
Cells, and Cells of Supporting Structures
In Light Microscopy:
o liver appears to be organized in lobules, with
portal areas at the periphery and central veins in
the center of each lobule
Functional point of view:
o liver is organized into acini, with both hepatic
arterial and portal venous blood entering the
acinus from the portal areas (zone 1) and then
flowing through the sinusoids to the terminal
hepatic veins (zone 3); the intervening
hepatocytes constitute zone 2
* advantage of viewing the acinus as the physiologic unit
of the liver is that this perspective helps to explain the
morphologic patterns and zonality of many vascular and
biliary diseases not explained by the lobular arrangement
Portal Areas of Liver
o consist of small veins, arteries, bile ducts, and
lymphatics organized in a loose stroma of
supporting matrix and small amounts of collagen
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 o Blood Flow (into portal areas): Zone 1 -> Zone 2 ->
Zone 3
*distributed through the sinusoids, passing from zone
1 to zone 3 of the acinus and draining into the
terminal hepatic veins (“central veins”)
o Bile Flow: Zone 3 -> Zone 2 -> Zone 1 (counter-
current pattern)
o Sinusoids - lined by unique endothelial cells that
have prominent fenestrae of variable sizes,
allowing the free flow of plasma but not of
cellular elements.
o Plasma - is in direct contact with hepatocytes in
the subendothelial space of Disse
LIVER DISEASES
CLASSIFICATION OF LIVER DISEASES
1. Hepatocellular diseases
o features of liver injury, inflammation, and
necrosis predominate
o such as viral hepatitis and alcoholic liver
disease
2. Cholestatic diseases,
o features of inhibition of bile flow predominate.
o such as gallstone or malignant obstruction,
primary biliary cholangitis (previously referred to
as primary biliary cirrhosis), and some drug-
induced liver diseases
3. Mixed pattern
o features of both hepatocellular and cholestatic
injury
o such as cholestatic forms of viral hepatitis and
many drug-induced liver diseases
* Pattern of onset and prominence of symptoms can
rapidly suggest a diagnosis, particularly if major risk
factors are considered, such as the age and sex of the
patient and a history of exposure or risk behaviors
TYPICAL PRESENTING SYMPTOMS OF LIVER
DISEASE
• jaundice
• fatigue
• itching
• right-upper-quadrant pain
• nausea
• poor appetite
• abdominal distention
• intestinal bleeding
EVALUATION OF PATIENTS WITH LIVER DSE
SHOULD BE DIRECTED TO:
1. Establishing the etiologic diagnosis
• Diagnosis: should focus on the category of
disease (hepatocellular, cholestatic, or mixed
injury) as well as on the specific etiologic
diagnosis
2. Estimating disease severity (grading)
• Grading: refers to assessment of the severity
or activity of disease—active or inactive as well
as mild, moderate, or severe
3. Establishing the disease stage (staging).
• Staging: refers to estimation of the point in
the course of the natural history of the disease,
whether early or late; or precirrhotic, cirrhotic, or
end-stage.
A. CLINICAL HISTORY
•FOCUS: Symptoms of liver disease (patterns of onset
& prog.)
Potential risk factors for liver disease
•MANIFESTATIONS:
1. Constitutional symptoms
→ such as fatigue, weakness, nausea, poor
appetite, &
malaise
→ more liver specific symptoms of jaundice,
dark urine,
light stools, itching, abdominal pain, and
bloating
•SYMPTOMS: can also suggest the presence of
cirrhosis, end-stage liver disease, or complications of
cirrhosis (i.e. portal hypertension)
•ETIOLOGY: consider constellation of symptoms and
their patterns
of onset rather than a specific symptom
C.M. IMPORTANT INFO
FATIGUE - most common and most characteristic sx
- described as lethargy, weakness, listlessness,
malaise, ↑ need for sleep, lack of stamina, and
poor energy
- in liver dse,
•typically arises after activity or exercise and
is rarely after adequate rest
- “afternoon” not “morning” fatigue
- often intermittent and variable in severity (hr-to-
hr & day-to-day)
- may not be clear whether it is d/t the liver dse
or other probs (i.e. stress, anxiety, sleep
disturbance, or a concurrent illness)
NAUSEA - occurs w/ more severe liver disease
- may accompany fatigue or be provoked by
smelling food odors or eating fatty foods
VOMITING - can occur but is rarely persistent or prominent
POOR - frequent in acute liver disease
APPETITE W/ - rare in chronic disease (except when cirrhosis
WEIGHT LOSS is present and advanced)
DIARRHEA - uncommon in liver disease (except with
severe jaundice) in w/c a lack of bile acids
reaching the intestine can lead to steatorrhea
RUQ - “liver pain”
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DISCOMFORT/ - occurs in many liver diseases 6. Exposure to jaundiced or other high-risk persons
ACHE - marked by tenderness over the liver area 7. Injection drug use
- pain arises from stretching or irritation of 8. Recent surgery
Glisson’s capsule (w/c surrounds the liver 9. Remote or recent transfusion of blood or blood
and is rich in nerve endings)
products
- Severe pain is most typical of: 10. Occupation
•gallbladder disease 11. Accidental exposure to blood or needlestick
•liver abscess 12. Familial history of liver disease
•severe sinusoidal obstruction syndrome
--- (previously known as veno-occlusive •VIRAL HEPATITIS
disease) -For assessing its risks, a careful history of sexual
•occasional accompaniment of acute hepatitis activity is
ITCHING - occurs with acute liver disease of particular importance and should include the:
- appearing:
1. Number of lifetime sexual partners
EARLY in obstructive jaundice
--- (from biliary obstruction or drug- 2. History of having sex with men (for males
induced cholestasis) only)
LATER in hepatocellular disease 3. Family hx of hepatitis, liver disease, and liver
--- (acute hepatitis) cancer
HEPA Sexual Maternal- Prevent vertical
- also occurs in chronic liver diseases typically exposure infant spread
the cholestatic forms such as: (for transmission
1. Primary biliary cholangitis spreading)
2. Sclerosing cholangitis Hepatitis common - Passive and
- often the presenting symptom, preceding the B mode active
onset of jaundice immunization of
the infant at birth
- can occur in any liver disease, particularly
once cirrhosis develops. - Addition of
JAUNDICE - hallmark symptom of liver disease & perhaps antiviral therapy
the most reliable marker of severity YES during the third
trimester of
- USUAL REPORT: darkening of the urine pregnancy is now
before they notice scleral icterus recommended for
mothers with
- rarely detectable with a bilirubin level <43 levels of HBV
μmol/L (2.5 mg/dL) DNA
- With severe cholestasis, there will also be >200,000 IU/mL
lightening stool color and steatorrhea. Hepatitis uncommon - No reliable
- if without dark urine, usually indicates: C means of
1) Indirect (unconjugated) hyperbilirubinemia prevention
- typical of hemolytic anemia -TRANSMISSION: more common among HIV-co-
2) Genetic disorders of bilirubin conjugation infected
Gilbert -common mothers & also linked to:
syndrome -benign form °prolonged and difficult labor and delivery
°early rupture of membranes
-5% of the gen. population
°internal fetal monitoring
- jaundice in this condition is
more noticeable after
°high viral load
fasting & with stress -HISTORY OF INJECTION DRUG USE: great
Crigler- -rare importance in
Najjar -severe form assessing the risk for hepatitis B and C
syndrome ! It’s now the single most common risk factor for hepa
C.
•MAJOR RISK FACTORS FOR LIVER DISEASE that -TRANSFUSION with blood or blood products: No
should be longer an
sought in the clinical history include details of: important risk factor for acute viral hepatitis
1. Alcohol use -RISK FACTORS for HEPATITIS A:
2. Medication use (including herbal compounds, °travel to a developing areas
birth control pills, °exposure to persons with jaundice
and over-the-counter °exposure to young children in day-care
medications) - Tattooing & body piercing (hepatitis B &quite C) rarely lead to
3. Personal habits Eating shellfish (hepatitis A) the acquisition of
hepatitis
4. Sexual activity
5. Travel - HEPATITIS E

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 - one of the more common causes of jaundice 2. Hemochromatosis and α1 antitrypsin deficiency
in Asia and - A family history of cirrhosis, diabetes, or endocrine
Africa (uncommon in developed nations) failure; and the appearance of liver disease in adulthood
- usually d/t fecally contaminated water suggests hemochromatosis and should prompt
- Recently, non-travel-related (autochthonous) investigation of iron status.
cases - Abnormal iron studies in adult pxs warrant
have been described in developed countries genotyping of the HFE gene for the C282Y and H63D
like US. mutations typical of genetic hemochromatosis.
*These cases appear to be due to strains of hepatitis E virus that are
endemic in swine and some wild animals (genotypes 3 and 4). - In children and adolescents with iron overload, other
- predominantly in elderly men without typical non-HFE causes of hemochromatosis should be sought.
risk factors for viral hepatitis and even exposure - A family history of emphysema should lead to
- can become chronic in immunosuppressed investigation of low α1 antitrypsin levels and for
individuals: protease inhibitor (Pi) genotype.
°transplant recipients 3. Inherited pediatric liver diseases (more uncommon)
°chemotherapy °Familial intrahepatic cholestasis
° w/ HIV infection “abnormal serum enzymes in the °Benign recurrent intrahepatic cholestasis
absence of markers of hepatitis B or C” °Alagille syndrome
B. PHYSICAL EXAMINATION
•ALCOHOL INTAKE •RARELY uncovers evidence of liver dysfunction in a
- important in assessing the cause of liver disease patient w/o
and also in symptoms or laboratory findings, nor are most signs of
planning management and recommendations liver
- associated with an increased rate of alcoholic liver disease specific to one diagnosis.
dse: •Thus, PE complements rather than replaces the need
Women- more than two drinks (22–30 g) per day for other
Men- more than three drinks (33–45 g) per day diagnostic approaches.
- Most patients w/ alcoholic cirrhosis have a much •In many patients, PE is normal unless the disease is
higher acute or
daily intake and excessively for ≥10 years before severe and advanced.
onset of •Nevertheless, PE is important in that it can yield the
liver disease. first evidence
- assess whether alcohol abuse or dependence is of hepatic failure, portal hypertension, and liver
present decompensation.
*Alcoholism- behavioral patterns and consequences of •In addition, PE can reveal signs—related either to risk
alcohol intake, not by the amount factors or to associated diseases or findings—that
*Abuse- repetitive pattern of drinking alcohol that has point to a specific dx.
adverse effects on social, family, occupational, or health •TYPICAL PHYSICAL FINDINGS in liver disease:
status - icterus - spider angiomata
*Dependence- alcohol-seeking behavior, despite its - hepatomegaly - palmar erythema
adverse effects - hepatic tenderness - skin excoriations
- more serious and advanced form of - splenomegaly
alcoholism •SIGNS OF ADVANCED DISEASE:
- CAGE questionnaire (dx of alcohol dependence - muscle wasting - mental confusion
& abuse) - ascites - stupor
- recommended for all medical history-taking - edema - coma
- dilated abdominal veins
- hepatic fetor, asterixis,
•MALE PATIENTS WITH CIRRHOSIS (alcohol use)
-Hyperestrogenemia such as:
°gynecomastia
°testicular atrophy
°loss of male-pattern hair distribution
Icterus •Best appreciated when the sclera is
•FAMILY HISTORY (Jaundice) inspected
- can be helpful in assessing liver disease under natural light
- Familial causes of liver disease include: •In fair-skinned individuals, a yellow tinge to
1. Wilson disease the skin may be obvious.
- Onset of severe liver disease in childhood or •In dark-skinned individuals, examination of
the mucous membranes below the tongue
adolescence in conjunction w/ a family history of liver
can demonstrate jaundice.
disease or neuropsychiatricdisturbance should lead to
investigation of this disease. Jaundice is rarely detectable if the serum

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 bilirubin level is <43 μmol/L (2.5 mg/dL) but *First signs of hepatic encephalopathy can be subtle
may remain detectable below this level and nonspecific:
during recovery from jaundice (because of -change in sleep patterns -irritability
protein and tissue binding of conjugated -change in personality -mental
bilirubin).
dullness
Spider •Both acute and chronic liver disease
angiomata •Prominent in persons with cirrhosis
*Thereafter these can supervene:
and palmar •But can develop in normal individuals and -confusion -stupor
erythema are -disorientation -coma
frequently found during pregnancy. - In acute liver failure, excitability and mania may
Spider •Superficial, tortuous arterioles be present.
angiomata •Unlike simple telangiectases, it’s typically fill - PHYSICAL FINDINGS include:
from the center outward *asterixis
•ONLY on the arms, face, and upper torso *flapping tremors of the body and tongue
•Can be pulsatile and may be difficult to - Fetor hepaticus- slightly sweet, ammoniacal odor
detect in dark-skinned individuals
that can
Hepatomegaly •NOT a highly reliable sign of liver disease
because of variability in the liver’s size and develop in pxs w/ liver failure, particularly if there is
shape and the physical impediments to portal-
assessment of liver size by percussion and venous shunting of blood around the liver.
palpation. - OTHER CAUSES OF COMA AND
•MARKED HEPATOMEGALY is typical of: DISORIENTATION should
- cirrhosis be EXCLUDED, mainly:
- sinusoidal obstruction syndrome *Electrolyte imbalances
- infiltrative disorders (i.e amyloidosis) *Sedative use
- metastatic/ primary cancers of the liver
*Renal or respiratory failure
- alcoholic hepatitis
•Careful assessment of the liver edge may - FULMINANT HEPATITIS: Its major criterion is the
also reveal: appearance
- unusual firmness of hepatic encephalopathy during acute
- irregularity of the surface hepatitis; and
- frank nodules indicates a poor prognosis.
•HEPATIC TENDERNESS- perhaps the - In chronic liver failure, encephalopathy is usually
most triggered
reliable physical finding in liver examination by a medical complication such as:
•DISCOMFORT when the liver is touched or
*Gastrointestinal bleeding *Electrolyte
pressed upon should be carefully sought
with imbalance
percussive comparison of the R & L *Over-diuresis *Infection
upper *Uremia *Constipation
quadrants. *Dehydration *Use of narcotic
Splenomegaly •Occurs in many medical conditions analgesics
•Can be a subtle but significant physical •HEPATIC ENCEPALOPATHY
finding in liver disease - a helpful measure of it is a careful mental status
•Ultrasound (US) methods for assessment exam and
of use of the trail-making test
the spleen allows confirmation of the
- TRAIL-MAKING TEST: consists of a series of 25
physical
finding. numbered
Signs of •ASCITES: Best appreciated by attempts to circles that the px is asked to connect as rapidly as
ADVANCED detect shifting dullness by careful possible
liver disease percussion. using a pencil
-muscle *US examination will confirm the *Normal: 15–30 sec
wasting finding of ascites in *Longer in pxs w/ early hepatic encephalopathy
-weight loss equivocal/ vague cases. - OTHER TESTS: include drawing of abstract objects
-hepatomegaly •PERIPHERAL EDEMA: can occur w/ or w/o or
-bruising ascites
comparison of a signature to previous examples
-ascites •ADVANCED LIVER DISEASE, other factors
-edema frequently contribute to edema formation: - MORE SOPHISTICATED TESTING: e.g. with
- hypoalbuminemia electro-
- venous insufficiency encephalography and visual evoked potentials
- heart failure - can detect mild forms of encephalopathy but are
- medications rarely clinically useful
•HEPATIC FAILURE •Other signs of ADVANCED liver disease:
- occurrence of signs or symptoms of hepatic - Umbilical hernia from ascites
encephalopathy - Hydrothorax
in a person with severe acute/chronic liver dse - Prominent veins over the abdomen

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 - caput medusa
- condition consists of collateral veins radiating from C. DIAGNOSIS
the umbilicus
- results from recanulation of the umbilical vein
•Most common causes- acute liver disease are:
•Widened pulse pressure can occur in patients w/ cirrhosis as a 1. Viral hepatitis (particularly hepatitis A, B, and C)
result of:
•Signs of a hyperdynamic circulation 2. Drug-induced liver injury
1. Fluid and sodium retention
2. Increased cardiac output 3. Cholangitis
3. Reduced peripheral resistance 4. Alcoholic liver disease
•LONG-STANDING CIRRHOSIS and PORTAL •LIVER BIOPSY
HYPERTENSION - usually is not needed in the dx & mgt of acute liver
- are prone to develop the hepatopulmonary disease
syndrome (w/c (except if dx remains unclear despite thorough
is defined by the: clinical and laboratory investigation)
1. Triad of liver disease - can be helpful in diagnosing drug-induced liver
2. Hypoxemia disease and
3. Pulmonary arteriovenous shunting acute alcoholic hepatitis
•Most common causes- chronic liver disease (in
•HEPATOPULMONARY SYNDROME is characterized gen.order of freq.):
by: 1. Chronic hepatitis C
• Platypnea 2. Alcoholic liver disease
• Orthodeoxia 3. Nonalcoholic steatohepatitis
-shortness of breath and oxygen desaturation that 4. Chronic hepatitis B
occur paradoxically upon the assumption of an upright 5. Autoimmune hepatitis
position 6. Sclerosing cholangitis
- measurement of oxygen saturation by pulse 7. Primary biliary cholangitis
oximetry is a reliable screening test for it 8. Emochromatosis
•Several skin disorders & changes are common in liver 9. Wilson disease
disease. 10. Hepatitis E (RARE) in
•HYPERPIGMENTATION: typical of advanced chronic immunosuppressed/immunodeficient pxs
cholestatic diseases (i.e 1° biliary cholangitis & •X Strict diagnostic criteria for most liver diseases, but
sclerosing cholangitis) liver biopsy
•In these same conditions, xanthelasma and tendon plays an important role in the diagnosis:
xanthomata 1. Autoimmune hepatitis
occur as a result of retention and high serum levels of 2. Primary biliary cholangitis
lipids and 3. Nonalcoholic & alcoholic steatohepatitis
cholesterol. 4. Wilson disease (w/ a quantitative hepatic copper level
•HEMOCHROMATOSIS: includes slate-gray in the last instance)
pigmentation of the
skin if iron levels are high for a prolonged period C.1 LABORATORY TESTING
•Mucocutaneous vasculitis with palpable purpura •Diagnosis of liver disease is greatly aided by the
(especially on the availability of
lower extremities) reliable and sensitive tests of liver injury and function.
- is typical of cryoglobulinemia of chronic hepatitis •A typical battery of blood tests used for initial
C, but can assessment of liver disease includes measurement of
also occur in chronic hepatitis B levels of:
•Some physical signs point to specific liver diseases. 1. Serum alanine (ALT) & Aspartate
SIGNS LIVER DISEASE & Other info aminotransferases (AST)
Kayser-Fleischer - occur in Wilson disease 2. Alkaline phosphatase (AlkP)
rings - consist of a golden-brown copper 3. Direct & Total serum bilirubin and albumin
pigment 4. Prothrombin time
deposited in Descemet’s
membrane at the
•Pattern of abnormalities:
periphery of the cornea 1. Gen. points to hepatocellular vs. cholestatic liver
- BEST seen by slit-lamp disease
examination. 2. Helps determine whether the dse is acute or
Dupuytren - are suggestive of chronic chronic
contracture and alcoholism and 3. Whether cirrhosis and hepatic failure are present
parotid enlargement alcoholic liver disease •On the basis of these results, further testing over time
Cachexia and wasting - signs of metastatic liver disease may be
(as well as firm or primary necessary.
hepatomegaly and a hepatocellular carcinoma
hepatic bruit may be •Other laboratory tests may be helpful, such as:
prominent) 1. γ-glutamyl transpeptidase (γ GT)

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 - to define whether AlkP elevations are due to liver -Also provides several
disease therapeutic options in
2. Hepatitis serology patients with obstructive
-to define the type of viral hepatitis jaundice i.e.:
•Sphincterotomy
3. Autoimmune markers
•Stone extraction
-to diagnose: •Placement of
a. Primary biliary cholangitis (antimitochondrial nasobiliary
antibody) catheters and biliary
b. Sclerosing cholangitis (peripheral antineutrophil stents
cytoplasmic antibody) •Doppler US and MRI
c. Autoimmune hepatitis (antinuclear, smooth- - assess hepatic vasculature and hemodynamics
muscle, & liver-kidney microsomal antibody) - monitor surgically or radiologically placed vascular
C.2 DIAGNOSTIC IMAGING shunts
•Still no method is adequately accurate in demonstrating including “transjugular intrahepatic portosystemic
underlying shunts”
cirrhosis in its early stages. •Multidetector or Spiral CT and MRI (w/ contrast-
enhancement)
Ultrasound -most commonly -highly sensitive for - procedures of choice for the identification and
(US) employed detecting “biliary duct
and are dilation”
evaluation of:
Computerized
tomography complementary to -1st line options for 1. Hepatic masses
(CT) one another “suspected obstructive 2. Staging of liver tumors
-can detect a fatty jaundice” 3. Preoperative assessment
Magnetic liver (appears CT & MRI •Mass lesions
resonance bright on imaging modifications - sensitivity of hepatic imaging continues to
imaging (MRI) studies) -can be used to increase
quantify liver fat - specificity remains a problem
*May ultimately be -often 2 & sometimes 3 studies are needed before
valuable in monitoring
a dx can be reached
therapy in pxs w/ fatty
liver disease •Contrast enhanced US
- an emerging imaging modality for the investigation of
Magnetic -Advantages over ERCP: hepatic
resonance •No need for contrast lesions
cholangiopancrea- media/ ionizing radiation - permits enhancement of liver lesions in a similar
tography (MRCP) •Images can be acquired fashion as contrast-enhanced, cross-sectional CT, or
faster MR imaging.
•Procedure is less - MAJOR ADVANTAGE: Real-time assessment of liver
operator perfusion throughout the vascular phases without risk of
dependent
nephrotoxicity and radiation exposure
•No risk of pancreatitis
-Superior to US and CT - OTHER ADVANTAGES: widespread availability and
for lower cost
choledocholithiasis - LIMITATIONS: Body habitus of the patient & skill of the
detection but less operator
specific. • US is the recommended modality for hepatocellular
procedures -Useful in the dx of bile
carcinoma screening.
of choice duct obstruction and
for congenital biliary • Contrast-enhanced US, CT, and MRI are appropriate
visualization abnormalities for further investigation of lesions detected on
Endoscopic of the -More valuable in screening US.
retrograde biliary tree evaluating ampullary • Liver Imaging Reporting and Data System (LI-
cholangiopancrea- lesions & 1° sclerosing RADS)
tography (ERCP) cholangitis -developed by the The American College of
-Permits: Radiologists
•Biopsy -to standardize the reporting and data collection of CT,
•Direct visualization of
the
MR, and contrast-enhanced US imaging for
ampulla & common bile hepatocellular carcinoma (HCC).
duct -allows for more consistent reporting and reduces
•Intraductal imaging interpretation variability and errors.
ultrasonography • US transient elastography
& brushings (for -approved for the measurement of hepatic stiffness—
cytological providing an indirect assessment of fibrosis and
evaluation of cirrhosis
malignancy)

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 -can eliminate the need for liver biopsy if the only
indication is the assessment of disease stage.
• MR elastography
-more sensitive than US elastography, but more
expensive and requires advanced scheduling and
special equipment.
* Studies are ongoing to determine whether hepatic
elastography is an appropriate means of monitoring fibrosis
and dse progression.
• Interventional radiologic techniques allow the
biopsy of solitary lesions, the radiofrequency ablation
and chemoembolization of cancerous lesions, the
insertion of drains into hepatic abscesses, the
measurement of portal pressure, and the creation of
vascular shunts in patients with portal hypertension.
• Which modality to use?
-depends on Availability, Cost, Experience of the
radiologist with each technique
C.3. LIVER BIOPSY
Liver biopsy - remains the gold standard in the
evaluation of patients with liver disease,
particularly chronic liver disease.
-necessary for diagnosis in selected
instances but is more often useful for
assessment of the
o severity (grade) and stage of liver
damage,
o prediction of prognosis
o monitoring of the response to treatment.
-Size of the liver biopsy sample- is an important
determinant of reliability; a length of 1.5–2 cm is
necessary for accurate assessment of fibrosis.
- liver biopsy is an invasive procedure and not without
complications, it should be used only when it will
contribute materially to decisions about management
and therapy
-In the future, noninvasive means of assessing disease
activity (batteries of blood tests) and fibrosis
(elastography and fibrosis markers) may replace liver
biopsy for the staging and grading of disease.
D. GRADING AND STAGING OF LIVER DISEASE
GRADING - refers to an assessment of the severity or
activity of liver disease, whether acute or
chronic; active or inactive; and mild, moderate,
or severe.
• Liver biopsy - most accurate means of assessing
severity, particularly in chronic liver disease.
-helpful in guiding management and identifying
appropriate therapy, particularly if treatment is
difficult, prolonged, and expensive, as is often
the case in chronic viral hepatitis
• Serum aminotransferase levels - serve as convenient
and noninvasive markers for disease activity but do
not always reliably reflect disease severity.
o Hepatitis B px w/ surface antigen in serum
-w/ normal serum aminotransferase levels may
indicate the inactive carrier state or may reflect
mild chronic hepatitis B or hepatitis B with
fluctuating disease activity
* Serum testing for hepatitis B e antigen and hepatitis B
virus DNA
-help sort out these different patterns, but these markers
can also fluctuate and change over time
o Chronic hepatitis C
-serum aminotransferase levels can be normal
despite moderate disease activity.
o Alcoholic and nonalcoholic steatohepatitis
-aminotransferase levels are quite unreliable in
reflecting severity
• Most commonly used well-verified numerical scales for
grading activity in chronic liver disease
o METAVIR
o histology activity index and the
o Ishak fibrosis scale.
STAGING
• Liver biopsy - also the most accurate means of
assessing stage of disease as early or advanced,
precirrhotic, and cirrhotic.
• Staging pertains largely to chronic liver diseases in
which progression to cirrhosis and end-stage disease
can occur but may require years or decades.
• Clinical features, biochemical tests, and hepatic
imaging studies are helpful in assessing stage but
generally become abnormal only in the middle to late
stages of cirrhosis.
• Noninvasive tests that suggest advanced fibrosis
o mild elevations of bilirubin
o prolongation of prothrombin time
o slight decreases in serum albumin
o mild thrombocytopenia (which is often the first
indication of worsening fibrosis)
• Combinations of blood test results that include clinical
features, routine laboratory tests, and special
laboratory tests such as serum proteins or small
molecules that are affected by or involved with
fibrogenesis have been used to create models for
predicting advanced liver disease
* but these models are not reliable enough to use on a reg-
ular basis or for repeated measures and only separate
advanced from early disease
• Elastography and noninvasive breath tests using 13C-
labeled compounds
-have been proposed as a means of detecting
early stages of fibrosis and liver dysfunction, but their
reliability and reproducibility remain to be proven.
-major limitation of noninvasive markers - can be
affected by disease activity.
-limitation of Elastography - it measures liver
stiffness, not fibrosis per se, and can be affected by
inflammation, edema, hepatocyte necrosis, and
intrasinusoidal cellularity (inflammatory, malignant, or
sickled cells).
-Thus, at present, only liver biopsy can detect
mild to moderate stages of hepatic fibrosis
• Assessment of stage - the degree of fibrosis is usually
used as the quantitative measure.
o The amount of fibrosis is generally staged on a
scale of 0 to 4+ (METAVIR scale) or 0 to 6+ (Ishak
scale).
D.AHA & A.HM
MSU-COM (Class 2023)
• Importance of staging relates primarily to
o prognosis
o recommendation of therapy
o to optimal management of complications
• Patients with cirrhosis are candidates for screening
and surveillance for esophageal varices and
hepatocellular carcinoma. Patients without advanced
fibrosis need not undergo screening.
SCORING SYSTEMS FOR ASSESSMENT OF
COMPENSATED VS. DECOMPENSATED DISEASE
AND PROGNOSIS once cirrhosis develops
• Modified Child- Pugh classification
o initial staging system used for assessing
compensated versus decompensated disease
and prognosis
o with a scoring system of 5–15:
- scores 5-6 -> Class A (consistent with
“compensated cirrhosis”)
- scores of 7–9 -> Class B
- scores of 10–15 -> Class C
o initially devised to stratify patients with cirrhosis
into risk groups before portal decompressive
surgery.
o reasonably reliable predictor of survival in many
liver diseases and predicts the likelihood of
major complications of cirrhosis, such as
bleeding from varices and spontaneous bacterial
peritonitis.
o used to assess prognosis in cirrhosis and to
provide standard criteria for listing a patient as a
candidate for liver transplantation (Child-Pugh
class B).
• Model for End-Stage Liver Disease (MELD) system
o replaced Child-Pugh system in providing
standard criteria for listing a patient as a
candidate for liver transplantation
o Meld Score – prospectively derived system
designed to predict the prognosis of patients
with liver disease and portal hypertension
o Initially, this score was calculated from three
noninvasive variables:
✓ the prothrombin time expressed as the
international normalized ratio (INR),
✓ the serum bilirubin level
✓ the serum creatinine concentration.
*The ability of the MELD score to predict outcome after
liver transplantation is regularly monitored and was
modified to increase its accuracy and improve allocation of
donated livers. These modifications include serum sodium
concentration as a factor in the model and a reweighting of
the MELD components.
• Pediatric end-stage liver disease (PELD) – used for
children (<12 years of age)
• Transient elastography
-has also been used to stage cirrhosis and has been
shown to be useful in predicting complications such as
variceal hemorrhage, ascites development and liver-
related death.
***The MELD system provides a more objective means
of assessing disease severity and has less center-to-
center variation than the Child-Pugh score as well as a
wider range of values. The MELD and PELD systems
are currently used to establish priority listing for liver
transplantation in the United States.
E. NONSPECIFIC ISSUES IN THE MANAGEMENT OF
PATIENTS WITH LIVER DISEASE
1. Alcohol use
- alcohol should be used sparingly, if at all, by patients
with liver disease.
- abstinence from alcohol should be encouraged for all
patients with alcohol-related liver disease, patients
with cirrhosis, and patients receiving interferon-based
therapy for hepatitis B and during antiviral therapy of
hepatitis C
2. Medication use
- Patients with liver disease should exercise caution in
using any medications other than those that are most
necessary
- Drug-induced hepatotoxicity can mimic many forms of
liver disease and can cause exacerbations of chronic
hepatitis and cirrhosis; drugs should be suspected in
any situation in which the cause of exacerbation is
unknown
3. Vaccination
- all patients with liver disease should receive
hepatitis A vaccine, and those with risk factors
should receive hepatitis B vaccine as well
- Influenza and pneumococcal vaccination should also
be encouraged, with adherence to the
recommendations of the Centers for Disease Control
and Prevention
4. Surveillance for complications of liver disease
- Complications such as variceal hemorrhage and
hepatocellular carcinoma
- Cirrhosis warrants:
- upper endoscopy to assess the presence of
varices, and
-chronic therapy with beta blockers or should
be offered
-endoscopic obliteration if large varices are
found
- screening and long-term surveillance for
development of hepatocellular carcinoma.
While the optimal regimen for such surveil-
lance has not been established, an
appropriate approach is US of the liver at 6- to
12-month intervals.
D.AHA & A.HM
MSU-COM (Class 2023)
 D.AHA & A.HM
MSU-COM (Class 2023)
 D.AHA & A.HM
MSU-COM (Class 2023)