1. Approach to the Patient with Liver Disease Chapter 301 Harrison 2012
Baghbanian M.
Gasteroentrologist
Sadughi hospital
1390/7/27

2. Diagnosis of liver disease is made by :
Careful history
Physical examination
Laboratory tests
Radiologic examinations
Liver biopsy
less for diagnosis than for grading and staging

3. Liver Structure and Function
largest organ of the body
1–1.5 kg
1.5–2.5% of lean body mass.
size and shape of the liver vary and match the general body shape

5. The liver is located in ?
RUQ under the right lower rib cage against the diaphragm and projects into the LUQ

6. The liver is held by ? Ligamentous attachments to the diaphragm
Peritoneum
Great vessels
Upper gastrointestinal organs

7. Liver blood supply? Dual blood supply:
20% : hepatic artery(oxygen-rich)
from celiac artery
80% : portal vein (nutrient-rich )
from stomach, intestines, pancreas, and spleen

10. Liver cells? The majority of cells : The remaining cell are:
hepatocytes (2/3 of the mass of the liver)
The remaining cell are:
Kupffer cells (reticuloendothelial system)
stellate (Ito or fat-storing) cells
endothelial cells and blood vessels
bile ductular cells

11. Liver structure?
In light microscopy: Lobules with portal areas at the periphery and central veins in the center of each lobule.

12. Portal areas? Consist of : small veins Arteries bile ducts lymphatics
organized in a loose stroma of matrix and collagen.

14. Acini? physiologic unit of the liver :
helps to explain the morphologic patterns and zonality of many vascular and biliary diseases not explained by the lobular arrangement.

15. Acini
fenestrae in sinusoids→ free flow of plasma but not cellular elements.
plasma is in direct contact with hepatocytes in the subendothelial space of Disse.

16. Acini Blood flowing: Bile flowing: zone 1 → zone 3 of the acinus
portal veins → hepatic (central ) veins
Bile flowing:
zone 3 → zone 1 of the acinus

18. Hepatocytes function? 1-synthesis of most proteins
(albumin, coagulation factors)
2-production of bile
(bile acids, cholesterol, phospholipids)
3-regulation of nutrients
(glucose, glycogen, lipids, amino acids)
4-metabolism and conjugation of compounds for excretion in bile or urine
(bilirubin, drugs)

19. most commonly liver "function" tests
Serum bilirubin
is a measure of hepatic conjugation and excretion
Albumin and prothrombin time
are measures of protein synthesis.
hepatic dysfunction: Abnormalities of bilirubin, albumin, and prothrombin time

20. liver disease patterns?
Hepatocellular diseases :
inflammation and necrosis
(viral hepatitis or alcoholic liver disease)
Cholestatic diseases:
inhibition of bile flow
(gallstone or malignancy , primary biliary cirrhosis)
Mixed pattern:
hepatocellular + cholestatic
( cholestatic forms of viral hepatitis and many drug-induced liver diseases).

21. Liver disease patterns is important?
pattern of onset + prominence of symptoms can rapidly suggest a diagnosis

23. symptoms of liver disease?
Fatigue Itching RUQ pain Nausea Poor appetite Abdominal distention GI bleeding

24. liver disease with no symptoms?
Many patients with liver disease are no symptomatic
Manifestaion : abnormalities in liver tests
As a part of a routine physical examination
Or screening for blood donation
Or for insurance or employment.

25. Diagnosis : HOW? 1- PATTERN of disease? 2- Specific ETIOLOGIC ?
(hepatocellular, cholestatic, or mixed injury)
2- Specific ETIOLOGIC ?
3- Grading ?
(severity or activity of disease—active or inactive, and mild, moderate, or severe)
4-Staging ?
(whether acute or chronic; early or late; precirrhotic, cirrhotic, or end-stage)

26. Clinical history should focus on symptoms of liver disease:
their nature
patterns of onset
patterns of progression
— potential risk factors for liver disease.

27. Clinical history Symptoms can also suggest the presence of:
cirrhosis and end-stage liver disease
complications of cirrhosis such as portal hypertension.

28. Fatigue
The most common and most characteristic symptom of liver disease.
Typically after activity or exercise
Rarely present or severe in the morning after adequate rest
afternoon versus morning

29. Nausea Vomiting Nausea occurs with more severe liver disease
May be provoked by odors of food or eating fatty foods.
Vomiting can occur but is rarely persistent or prominent.

30. Poor appetite with weight loss
Poor appetite with weight loss occurs commonly in acute liver diseases but
is rare in chronic disease
Except advanced cirrhosis

31. Diarrhea Diarrhea is uncommon in liver disease
Except with severe jaundice
lack of bile acids can lead to steatorrhea

32. RUQ pain
RUQ pain occurs in many liver diseases and is usually marked tenderness
The pain arises from stretching or irritation of Glisson's capsule, which is rich in nerve endings.

33. Severe RUQ pain Is most typical of:
Gallbladder disease
Liver abscess
Severe venoocclusive disease
Occasional accompaniment of acute hepatitis.

34. Itching acute liver disease chronic liver diseases
early in obstructive jaundice
later in hepatocellular disease (acute hepatitis).
chronic liver diseases
cholestatic disease (PSC and PBC) occur before the onset of jaundice
Itching can occur in any liver disease, particularly cirrhosis

35. Jaundice
hallmark symptom of liver disease and perhaps the most reliable marker of severity. Patients usually report darkening of the urine before scleral icterus. Jaundice is rarely detectable in bilirubin level <2.5 mg/dL.

36. severe Jaundice With severe cholestasis :
lightening of the color of the stools
steatorrhea

37. Jaundice without dark urine
Usually indicates indirect hyperbilirubinemia :
Hemolytic anemia
Genetic disorders of bilirubin conjugation
Gilbert's syndrome : common and benign
Crigler-Najjar syndrome:rare and severe
Gilbert's syndrome affects 5% of the population; jaundice is more : after fasting and stress.

38. Risk factors for liver disease
Personal habits ( Alcohol use , Injection drug use)
Medications ( herbal , OCP, and over-the-counter)
Sexual activity
Exposure to jaundiced or other high-risk persons
Recent surgery
Remote or recent blood products transfusion
Occupation
Accidental exposure to blood or needlestick
Familial history of liver disease.

39. assessing the risk of viral hepatitis
Careful history of sexual activity include:
the number of sexual partners
for men, a history of sex with men.
Sexual exposure is :
common mode of spread of hepatitis B
rare for hepatitis C

40. Assessing the risk of viral hepatitis
A family history of hepatitis, liver disease, and liver cancer is also important.
Maternal-infant transmission occurs with both hepatitis B and C
Vertical spread of HBV can now be prevented by passive and active immunization of the infant at birth

41. Vertical spread of hepatitis C
Is uncommon
There are no reliable means of prevention
Transmission is more common in :
HIV-co-infected mothers
Prolonged and difficult delivery
Early rupture of membranes
Internal fetal monitoring

42. History of injection drug use
Even in the remote past, is important for hepatitis B and C.
Injection drug use is now the single most common risk factor for hepatitis C

43. Blood transfusion
Transfusion with blood products is no longer an important risk factor for acute viral hepatitis
Before :
1992 is important risk factor for hepatitis C.
HCV Ab didn’t checked
1986 is a risk factor for hepatitis B.
anti-HBc didn’t checked

44. Risk factors for hepatitis A
Travel to an underdeveloped area of the world
Exposure to persons with jaundice
Exposure to young children in day-care centers
Eating shellfish(rare)

45. Risk factors for Hepatitis E
Is more common in Asia and Africa Eating raw or undercooked pork or game (deer and wild boars)

46. Tattooing and body piercing?
For hepatitis B and C are frequently mentioned but are actually quite rare types of exposure

47. Alcohol
In the United States,70% of adults drink alcohol , but significant alcohol intake is less common more than 2 drinks (22–30 g) per day in women 3 drinks (33–45 g) in men a A Alcoholic liver disease drunk for 10 years

48. Family history Familial causes of liver disease include:
Wilson's disease
Hemochromatosis
Alfa 1 antitrypsin deficiency
Familial intrahepatic cholestasis
Benign recurrent intrahepatic cholestasis
Alagille syndrome.

49. Wilson's disease
Severe liver disease in childhood or adolescence with a family history of liver disease or neuropsychiatric disturbance investigation for Wilson's disease

50. Hemochromatosis Liver disease in adulthood WITH:
Family history of cirrhosis
Diabetes
Endocrine failure
investigation of iron status

51. Hemochromatosis
Adult patients with abnormal iron studies genotyping of the HFE gene for the C282Y and H63D mutations

52. Alfa1 ATD A family history of emphysema + liver disease
investigation of 1AT levels
if low →Pi genotype

53. Physical examination
Complements rather than replaces the need for other diagnostic approaches.
Is normal In many patients unless the disease is acute or severe and advanced.
Can reveal signs that point to a specific diagnosis, either in risk factors or diseases .

54. Physical examination
Typical physical findings in liver disease are: Icterus Hepatomegaly Hepatic tenderness Splenomegaly Spider angiomata Palmar erythema Excoriations

55. Signs of advanced liver disease?
Muscle wasting
Ascites and edema
Dilated abdominal veins
Hepatic fetor
Asterixis
Mental confusion
Stupor and coma.
Bruising

56. signs of hyperestrogenemia
Males with cirrhosis
Particularly when related to alcohol
signs of hyperestrogenemia
(gynecomastia, testicular atrophy, and loss of male-pattern hair distribution )

57. Physical examination - Icterus
Sclera under natural light.
fair-skinned individuals : yellow skin may be obvious
dark-skinned individuals, the mucous membranes below the tongue demonstrate jaundice.
Jaundice is rarely detectable if the serum bilirubin level is < (2.5 mg/dL) but may remain detectable below this level during recovery from jaundice (protein and tissue binding of bilirubin).

59. Spider angiomata and palmar erythema
occur in:
Acute liver disease
Chronic liver disease
Especially prominent in cirrhosis
Occur in normal individuals and are frequently during pregnancy

60. Spider angiomata? Superficial, tortuous arterioles
fill from the center outward.
only on the arms, face, upper torso
Pulsatile and difficult to detect in dark-skinned individuals

64. Hepatomegaly Is not a very reliable sign of liver disease
(variability of the size and shape)
Marked hepatomegaly is typical :
Cirrhosis
Venoocclusive disease
Infiltrative disorders (amyloidosis, metastatic or primary cancers of the liver,alcoholic hepatitis.)

65. Hepatomegaly
Careful assessment of the liver edge may also demonstrate unusual:
Firmness
Irregularity of the surface
Frank nodules

66. Splenomegaly
occurs in many medical conditions but can be a significant physical finding in liver disease.
The availability of ultrasound (US) assessment of the spleen allows for confirmation of the physical finding.

68. Ascites
Ascites is best appreciated by attempts to detect shifting dullness by careful percussion.
US examination will confirm the finding of ascites in equivocal cases.

69. Edema ; causes? Hypoalbuminemia Venous insufficiency Heart failure
Medications(NSAID)

70. Hepatic failure?
signs or symptoms of hepatic encephalopathy in a person with severe acute or chronic liver disease. .

71. first signs of hepatic encephalopathy ?
change in sleep patterns and personality
irritability
mental dullness
In acute liver failure:
mania may be present

73. Physical findings Hepatic failure?
asterixis and flapping tremors of the body and tongue.
Fetor hepaticus :
slightly sweet, ammoniacal odor
in patients with liver failure
particularly portal-venous shunting of blood

75. Other causes of coma
Electrolyte imbalances Sedative use Renal failure Respiratory failure should be excluded in liver disease

76. Hepatic encephalopathy in acute hepatitis
Is major criterion for:
Diagnosis of fulminant hepatitis
Indicates a poor prognosis.

77. Hepatic encephalopathy In chronic liver disease
usually triggered by a medical complication :
GIB
Over diuresis
Uremia and electrolyte imbalance
Dehydration
Infection
Constipation
Narcotic analgesics.

79. Hepatic encephalopathy examination?
Connect a series of 25 numbered circles rapidly using a pencil.
The normal range is 15–30 seconds
delayed in patients with early encephalopathy.
drawing abstract objects
comparison of signature to previous.

80. Other signs of advanced liver disease
Umbilical hernia from ascites
Hydrothorax
Prominent veins over the abdomen
Caput medusa
resulting from the recanulation of the umbilical vein.
hyperdynamic circulation
Widened pulse pressure

81. Hyperdynamic circulation
cirrhosis
fluid and sodium retention
increased cardiac output
reduced peripheral resistance
hyperdynamic circulation
Widened pulse pressure

82. Hepatopulmonary syndrome?
In patients with long-standing cirrhosis and portal hypertension
Defined by triad :
liver disease
hypoxemia
pulmonary arteriovenous shunting.

83. Hepatopulmonary syndrome examination?
Characterized by:
platypnea
orthodeoxia
shortness of breath and oxygen desaturation that occur paradoxically in upright position
pulse oximetry is reliable screening test

84. Skin disorders in liver disease
Hyperpigmentation in: chronic cholestatic diseases (PBCand PSC)
Xanthelasma and tendon xanthomata as result of retention of lipids and cholesterol.
Gray pigmentation occurs with hemochromatosis
Mucocutaneous vasculitis with palpable purpura :typical of cryoglobulinemia of HCV but also occur in HBV.

85. Specific physical signs in liver disease
Kayser-Fleischer ring
in Wilson's disease
golden-brown copper in Descemet's membrane at periphery of the cornea
best seen by slit-lamp examination.
Dupuytren contracture , parotid enlargement
suggestive of alcoholic liver disease

86. Laboratory Testing Tests of liver injury: Tests of liver function:
ALT , AST
AlkP
Bilirubin
Tests of liver function:
Albumin
Prothrombin time.

87. Further testing may be necessary:
Gama glutamyl transpeptidase (gGT)
ALP elevations is due to liver disease?
Viral hepatitis serology
Markers of PBC (AMA)
Markers of sclerosing cholangitis (P-ANCA)
Markers of AIH(antinuclear, smooth-muscle, liver-kidney microsomal Ab).

88. Diagnostic Imaging US and CT:
Have a high sensitivity for detecting biliary duct dilatation
First-line options in patient with obstructive jaundice.

89. Imaging in Fatty liver
All three modalities can detect a fatty liver, which appears bright
CT and MRI in fatty liver :
quantify liver fat
monitoring therapy

90. visualization of the biliary tree
MRCP offers several advantages over ERCP
no need for contrast media or radiation
images can be acquired faster
less operator dependent
no risk of pancreatitis.
MRCP:
is superior to US and CT for choledocholithias
It is useful in congenital biliary abnormalities.

91. visualization of the biliary tree
ERCP:
is more valuable in ampullary lesions and PSC
allows for biopsy , direct visualization of the ampulla and CBD, intraductal SONO.
provides several therapeutic options in obstructive jaundice (sphincterotomy, stone extraction, and placement of nasobiliary catheters and biliary stents.)

92. Hepatic vasculature imaging
Doppler US and MRI are used to assess:
hepatic vasculature and hemodynamics
monitor surgically or radiologically placed vascular shunts such as transjugular intrahepatic portosystemic shunts.

93. Diagnostic Imaging in hepatic masses
CT and MRI are indicated for the evaluation of :
hepatic masses
staging of liver tumors
preoperative assessment
sensitivity is high
specificity remains a problem
two and sometimes three studies are needed

94. Diagnostic Imaging -elastography
Measure hepatic stiffness as a means of assessing hepatic fibrosis
US and MR elastrography
Detect hepatic fibrosis
Obviate the need for liver biopsy
Elastography may be an appropriate means of monitoring fibrosis and disease progression

95. Interventional radiologic techniques
-Biopsy of lesions
radiofrequency ablation
Chemoembolization of cancer
Insertion of drains into hepatic abscesses
Measurement of portal pressure
vascular shunts

96. Liver Biopsy
The criterion standard in the evaluation of liver disease, particularly chronic liver diseases.
Is necessary for diagnosis sometimes
Is more useful in:
Assessing the severity (grade and stage)
Predicting prognosis
Monitoring response to treatment

97. Liver Biopsy
The size of the liver biopsy length of 1.5–2 cm is necessary for accurate assessment of fibrosis.
noninvasive means of assessing disease activity ( blood tests) and fibrosis (elastography ) may replace liver biopsy in assessing stage and grade of disease.

98. Liver Biopsy
Usually not needed in the diagnosis and management of acute liver disease
exceptions that diagnosis remains unclear despite thorough clinical and laboratory investigation.
Is helpful in the diagnosis of:
Drug-induced liver disease
acute alcoholic hepatitis.

99. Liver Biopsy liver biopsy plays an important role in the diagnosis of:
Autoimmune hepatitis
Primary biliary cirrhosis
Nonalcoholic steatohepatitis
Alcoholic steatohepatitis
Wilson's disease (quantitative hepatic copper )
Strict diagnostic criteria have not been developed for most liver diseases

100. Liver Biopsy
liver biopsy is an invasive procedure and not without complications → should be used only when contribute to management and therapeutic decisions

101. For patients with suspected liver disease
1- initial testing for routine liver tests such as bilirubin, albumin, ALT, AST, AlkP 2-These results will establish whether the pattern of abnormalities is hepatic, cholestatic, or mixed.

102. For patients with suspected liver disease whether the disease is acute or chronic?
If the disease is acute and if history, laboratory tests, and imaging studies do not reveal a diagnosis liver biopsy establish the diagnosis.
If the disease is chronic liver biopsy can be helpful not only for diagnosis but also to grade the activity and stage the progression of disease.

103. liver disease evaluation in Immunocompromized patients
In patients with HIV infection or after bone marrow or solid organ transplantation, 1- evaluation of opportunistic infections (adenovirus, cytomegalovirus, coccidioidomycosis) 2- vascular and immunologic conditions (venoocclusive disease, graft-versus-host disease).

104. Causes of chronic liver disease?
The most common Causes are :
Chronic hepatitis C
Alcoholic liver disease
Nonalcoholic steatohepatitis
Chronic hepatitis B
Autoimmune hepatitis
Sclerosing cholangitis
Primary biliary cirrhosis
Hemochromatosis
Wilson's disease.

105. Grading
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 is the most accurate means of assessing severity, particularly in chronic liver disease.

106. Serum aminotransferase levels
Noninvasive means to follow disease activity, But not always reliable in reflecting disease severity.

107. Normal aminotransferase levels in HBsAg(+) patients
Indicate:
Inactive HBsAg carrier state or
Mild chronic hepatitis B or
Fluctuating disease activity
Serum testing for:
Hbe antigen
HBV DNA
(can help resolve these different patterns)
but these markers can also fluctuate and change over time.

108. Serum aminotransferase levels in chronic hepatitis C
Similar to hepatitis B , serum aminotransferase levels can be normal despite moderate activity of hepatitis C disease.

109. Serum aminotransferase levels in steatohepatitis
In alcoholic and nonalcoholic steatohepatitis:
aminotransferase levels are quite unreliable in reflecting severity.
In these conditions, liver biopsy is helpful in guiding and recommending therapy

110. scales for grading activity in chronic liver disease
The most common are:
Histology activity index
Ishak histology scale.
The amount of fibrosis is generally staged on:
0 to 4+ in Metavir scale
0 to 6+ scale in Ishak scale

111. Staging in chronic liver diseases
staging=amount of fibrosis the most accurate method :Liver biopsy Early stage staging precirrhotic Cirrhotic Mild to moderate stages of hepatic fibrosis are detectable only by liver biopsy.

112. importance of staging? Prognosis Guiding management of complications
Cirrhotic Patients are candidates for :
Screening and surveillance for:
Esophageal varices
Hepatocellular carcinoma

113. Cirrhosis can be staged clinically?
Child-Pugh classification is reliable staging system : (from 5–15) 5 and 6 → class A (compensated cirrhosis) 7–9 → indicating class B 10–15 → indicating class C . This scoring system was initially devised to stratify patients into risk groups prior to undergoing portal decompressive surgery.

114. Child-Turcotte-Pugh Scoring of Liver Disease Severity

115. importance of Child-Pugh score
Reliable predictor of survival in liver diseases
Predicts the likelihood of major complications of cirrhosis such as bleeding from varices and spontaneous bacterial peritonitis.
Assess prognosis in cirrhosis
Provide the standard criteria for listing liver transplantation

116. Child-Pugh score of >7 (class B)
Decompensation of cirrhosis listing liver transplantation.

117. M×odel for end-stage liver disease (MELD score)
Assessing for liver transplantation:
Child-Pugh system MELD score
Less center-to-center variation
More objective
Three noninvasive variables:
INR
serum bilirubin
serum creatinine

118. PELD (pediatric end-stage liver disease )
Children below the age of 12 years
Using :
Bilirubin
INR
Serum albumin
Age
Nutritional status

119. Nonspecific Issues in Management of Patients with Liver Disease
Alcohol use
Medications
Vaccination
Surveillance for complications of liver disease

120. Management of Alcohol use Patients with Liver Disease
Alcohol should be used sparingly, by patients with liver disease.
Abstinence should be encouraged for:
all alcohol-related liver disease
cirrhosis
receiving interferon-based therapy for hepatitis B or C.

121. Vaccinations in Patients with Liver Disease
All patients with liver disease should receive:
HAV vaccine
Those with risk factors should receive;
HBV vaccine
should also be encouraged:
Influenza vaccine
pneumococcal vaccine

122. Medications in Patients with Liver Disease
Patients with liver disease should be careful using any medications, other than the most necessary.
Drug-induced hepatotoxicity can:
Mimic many forms of liver disease
Exacerbate of chronic hepatitis and cirrhosis
Drugs should be suspected in which the cause of exacerbation is unknown

123. surveillance for complications of chronic liver disease
Variceal hemorrhage
upper endoscopy
Patients with cirrhosis: endoscopic obliteration
beta blocker
Hepatocellular carcinoma:
Patients with cirrhosis
US of the liver at 6- to 12-month intervals.

125. Healthy Liver
Hepatic Fibrosis
Cirrhosis
Liver Cancer

126. THE END

137. Macronodular cirrhosis

138. Micronodular cirrhosis

150. Visible signs of advanced liver cirrhosis
Gynecomastia
Ascites
Caput Medusae
Umbilical hernia