abnormal alt week 3 big group discussion 1. overview of liver function tests group d viardo-zuniga
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ABNORMAL ALT
Week 3 Big Group Discussion 1
Overview of Liver Function Tests
Group DViardo-Zuniga
Evaluation of Liver FunctionTests used to:
Detect presence of liver disease
Distinguish among different types of liver disorders
Gauge the extent of known liver damage
Follow the response to treatment
Evaluation of Liver FunctionLiver tests
Can be normal in patients with serious liver disease & abnormal in patients with diseases that do not affect the liver.
Rarely suggest a specific diagnosis; they suggest a general category of liver disease.
Evaluation of Liver FunctionTo increase sensitivity and specificity of
laboratory tests in the detection of liver disease, it is best to use them as a battery.
Tests usually employed in clinical practice: Bilirubin, aminotransferases (ALT, AST), alkaline
phosphates, albumin, and PT tests.
If more than one test provides abnormal findings, or are persistently abnormal on serial determinations, the probability of liver disease is high & vice versa
Tests Based on Detoxification &
Excretory Functions
Tests That Measure Biosynthetic Function Of The Liver
Other diagnostic tests
1.Serum Bilirubin2.Urine Bilirubin3. Blood Ammonia4. Serum Enzymes - ALT - AST
1. Serum Albumin2. Serum Globulin3. Coagulation Factors
1. Percutaneous Liver Biopsy2. Ultrasonography3. Ultrasonography with Doppler Imaging
Evaluation of Liver Function
Tests Based on Detoxification &
Excretory Functions
Tests That Measure Biosynthetic Function Of The Liver
Other diagnostic tests
1.Serum Bilirubin2.Urine Bilirubin3. Blood Ammonia4. Serum Enzymes - ALT - AST
1. Serum Albumin2. Serum Globulin3. Coagulation Factors
1. Percutaneous Liver Biopsy2. Ultrasonography3. Ultrasonography with Doppler Imaging
Evaluation of Liver Function
Tests Based on Detoxification & Excretory FunctionsSerum Bilirubin
Urine Bilirubin
Blood Ammonia
Serum Enzymes
Serum BilirubinUnconjugated bilirubin
Normal total serum bilirubin concentration is <17 mol/L (1 mg/dL)
Rarely due to liver disease, seen primarily in hemolytic disorders and genetic conditions such as Crigler-Najjar and Gilbert's syndromes
Urine Bilirubin
Conjugated bilirubin
(+) bilirubinuria implies the presence of liver disease
Dipstick test or Ictotest tablet used
Phenothiazines may give a false-positive reading with the Ictotest tablet
Blood Ammonia Normal protein metabolism and by intestinal
bacteria in the colon
Patients with advanced liver disease have significant muscle wasting, which contributes to hyperammonemia
Poor correlation w/ hepatic function. Ammonia can be elevated in patients with severe portal hypertension and portal blood shunting around the liver even in the presence of normal hepatic function.
Elevated arterial ammonia levels correlate with outcome in fulminant hepatic failure.
Serum EnzymesSerum enzyme tests can be grouped into three
categories: Enzymes that reflects damage to hepatocytes Enzymes that reflects cholestasis Enzyme tests that do not fit precisely into either
pattern
Enzymes that reflect hepatocyte damage
Aminotransferases Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Aminotransferases
Released into the blood in greater amounts when there is damage to the liver cell membrane resulting in increased permeability
Sensitive indicators of liver cell injury and most helpful in recognizing acute hepatocellular diseases (hepatitis)
Aminotransferases
Aspartate aminotransferase (AST) Found in the liver, cardiac muscle, skeletal muscle, kidneys, brain,
pancreas, lungs, leukocytes & erythrocytes ( order of concentration)
Alanine aminotransferase (ALT) Found primarily in the liver
Aminotransferase
Any type of liver cell injury can cause modest elevations in the serum aminotransferases
Levels of up to 300 U/L are nonspecific and may be found in any type of liver disorder
Striking elevations (> 1000 U/L) occurs almost exclusively in disorders associated with extensive hepatocellular injury Eg. viral hepatitis, ischemic liver injury, toxin-
induced liver injury or drug-induced liver injury
Aminotransferases In most acute hepatocellular disorders ALT is
or = to the AST
AST:ALT ratio > 2:1 is suggestive while a ratio > 3:1 is highly suggestive of alcoholic liver disease
AST in alcoholic liver disease is rarely >300 U/L and the ALT is often normal
ALT in serum is due to alcohol-induced deficiency of pyridoxal phosphate
Enzymes that Reflect CholestasisElevated in cholestasis
Alkaline Phosphatase 5'-nucleotidase Glutamyl Transpeptidase (GGT)
Alkaline PhosphataseNormal serum levels consists of distinct
isoenzymes found in the liver, bone, placenta
Normal non-pathologic found in: Over age 60 (1–1½ times normal) Blood types O and B: after eating a fatty meal Children and adolescents undergoing rapid bone
growth Late in normal pregnancies: influx of placental
alkaline phosphatase
Alkaline Phosphatase• > four times normal occur in:
– Cholestatic liver disorders
– Infiltrative liver diseases (cancer and amyloidosis)
– Bone conditions characterized by rapid bone turnover (Paget's disease)
• In the absence of jaundice or elevated aminotransferases, an elevated alkaline phosphatase of liver origin often, but not always, suggests early cholestasis
Alkaline PhosphataseOther conditions that cause isolated elevations
of the alkaline phosphatase include Hodgkin's disease, diabetes, hyperthyroidism, congestive heart failure, amyloidosis, and inflammatory bowel disease
5'-nucleotidase or GGT
Rarely elevated in conditions other than liver disease
GGT Good:
more sensitive marker for cholestatic damage than ALP. Helpful in identifying cause of isolated elevation in ALP
Raised in alcohol toxicity (acute and chronic). Bad:
elevated with even minor, sub-clinical levels of liver dysfunction
5'-nucleotidase Specific for cholestasis or damage to the intra or extrahepatic
biliary system
Tests Based on Detoxification &
Excretory Functions
Tests That Measure Biosynthetic Function Of The Liver
Other diagnostic tests
1.Serum Bilirubin2.Urine Bilirubin3. Blood Ammonia4. Serum Enzymes - ALT - AST
1. Serum Albumin2. Serum Globulin3. Coagulation Factors
1. Percutaneous Liver Biopsy2. Ultrasonography3. Ultrasonography with Doppler Imaging
Evaluation of Liver Function
Serum Albumin
Serum Globulins
Coagulation Factors
TESTS THAT MEASURE BIOSYNTHETIC FUNCTION OF THE
LIVER
Serum Albumin synthesized exclusively by hepatocytes has a long half-life: 18 to 20 days, with
approximately 4% degraded per day not a good indicator of acute or mild hepatic
dysfunction In hepatitis, albumin levels <3 g/dL = possible
chronic liver disease hypoalbuminemia is common in cirrhosis and
reflects severe liver damage and decreased albumin synthesis
In ascites, synthesis may be normal or increased, but in low levels =increased volume of distribution
hypoalbuminemia may occur in protein malnutrition of any cause, as well as protein-losing enteropathies, nephrotic syndrome, and chronic infections
Harrison’s Principle of Internal Medicine, 17th ed.
Serum Globulins Made up of:
gamma globulins (immunoglobulins) produced by B lymphocytes and alpha and beta globulins produced primarily in hepatocytes.
Gamma globulins are increased in chronic hepatitis and cirrhosis.
In cirrhosis, the increased serum gamma globulin concentration is due to increased synthesis of antibodies
Diffuse polyclonal increases (increases > 100%) in IgG
levels are common in autoimmune hepatitis.
Increases in the IgM levels are common in primary biliary cirrhosis.
Increases in the IgA levels occur in alcoholic liver disease Harrison’s Principle of Internal Medicine,
17th ed.
Coagulation Factors • With the exception of factor VIII, the blood clotting factors
are made exclusively in hepatocytes
• Their serum half-lives range from 6 h for factor VII to 5 days for fibrinogen
• Measurement of the clotting factors is the single best acute measure of hepatic synthetic function and helpful in both the diagnosis and assessing the prognosis of acute parenchymal liver disease
• Useful for this purpose is the serum prothrombin time, which measures factors II, V, VII, and X.
• Biosynthesis of factors II, VII, IX, and X depends on vitamin K.
• Prothrombin time is elevated in hepatitis and cirrhosis as well as in obstructive jaundice or fat malabsorption of any kind.
• Marked prolongation of the prothrombin time, >5 s above control and not corrected by parenteral vitamin K administration, is a poor prognostic sign in acute viral hepatitis and other acute and chronic liver diseases.
Harrison’s Principle of Internal Medicine, 17th ed.
Harrison’s Principle of Internal Medicine, 17th ed.
Tests Based on Detoxification &
Excretory Functions
Tests That Measure Biosynthetic Function Of The Liver
Other diagnostic tests
1.Serum Bilirubin2.Urine Bilirubin3. Blood Ammonia4. Serum Enzymes - ALT - AST
1. Serum Albumin2. Serum Globulin3. Coagulation Factors
1. Percutaneous Liver Biopsy2. Ultrasonography3. Ultrasonography with Doppler Imaging
Evaluation of Liver Function
Other diagnostic testsPreviously discussed tests direct the physician
to the category of the liver disease
Other radiologic testing and procedures are often necessary to make the proper diagnos
Percutaneous Liver BiopsySafe, bedside procedure
Most accurate in disorders causing diffuse changes in the liver
Of proven value in the following situationsHepatocellular disease of uncertain causeProlonged hepatitis with the possibility of chronic
active hepatitisUnexplained hepatomegalyUnexplained SplenomegalyHepatic filling defects by radiologic imagingFUOStaging of malignant lymphoma
Percutaneous Liver Biopsy
Contraindications
Significant ascites
Prolonged INR
Ultrasonography
First diagnostic test to use in patients whose liver tests suggest cholestasis
Determine presence of a dilated intrahepatic or extrahepatic biliary tree
Identification of gallstones
Space occupying lesion
Distinguish between solid and cystic masses
Helps direct percutaneous biopsies
Ultrasonography with Doppler ImagingFirst test ordered in patients suspected of
having Budd-Chiari syndrome
Detect patency of portal vein, hepatic artery, hepatic veins and determination of direction of blood flow
Use of Liver Tests
To increase the sensitivity and specificity of lab tests in the detection of liver disease a battery of tests is used
No single set of liver tests will necessarily provide a diagnosis
Necessary to repeat liver tests to a diagnostic pattern to emmerge
Hepatitis BHepatitis CHepatitis D
HBV HCV HDVIncubation
(days)30-180, mean
60-9015-160, mean
5030-180, mean
60-90
Onset Insidious or acute
insidious Insidious or acute
Age preference
Young adults, babies, toddlers
Any age, more common in
adults
Any age (same as HBV)
Transmission Percutaneous, perinatal, sexual
Percutaneous Percutaneous, non-
percutaneous
Severity Occasionally severe
moderate Occasionally severe
Fulminant 0.1-1% 0.1% 5-20%
Progression to chronicity
Occasional (1-10%) (90% of
neonates)
Common (85%) Common
Carrier 0.1-30% 1.5-3.2% Variable
Cancer + + +/-
Prognosis Worse with age Moderate Chronic - poor
Likelihood of chronicity after acute infection varies as a function of age.
More common in those who present with chronic infection without having experienced an acute illness neonatal infection infection in immunocompromised host
Most cases of chronic Hepatitis B among adults occur in patients who never had a recognized episode of clinically apparent acute viral hepatitis
HBV HCV HDV
Incubation (days)
30-180, mean 60-90 15-160, mean 50 30-180, mean 60-90
Onset Insidious or acute insidious Insidious or acute
Age preference Young adults, babies, toddlers
Any age, more common in adults
Any age (same as HBV)
Transmission Percutaneous, perinatal, sexual
Percutaneous Percutaneous, non-percutaneous
Severity Occasionally severe moderate Occasionally severe
Fulminant 0.1-1% 0.1% 5-20%
Progression to chronicity
Occasional (1-10%) (90% of neonates)
Common (85%) Common
Carrier 0.1-30% 1.5-3.2% Variable
Cancer + + +/-
Prognosis Worse with age Moderate Chronic - poor
A very slow and insidious process
Common even in those with a return to normal in aminotransferase levels after acute hepatitis C
Hepatitis C accounts for 40% of chronic liver disease (the most frequent indication for liver transplantation)
20-30% of patients with chronic hepatitis C will develop cirrhosis over 20-30 years
However, long term prognosis for majority is benign (asymptomatic & well compensated)
HBV HCV HDV
Incubation (days)
30-180, mean 60-90
15-160, mean 50 30-180, mean 60-90
Onset Insidious or acute insidious Insidious or acute
Age preference
Young adults, babies, toddlers
Any age, more common in adults
Any age (same as HBV)
Transmission Percutaneous, perinatal, sexual
Percutaneous Percutaneous, non-percutaneous
Severity Occasionally severe
moderate Occasionally severe
Fulminant 0.1-1% 0.1% 5-20%
Progression to chronicity
Occasional (1-10%) (90% of
neonates)
Common (85%) Common
Carrier 0.1-30% 1.5-3.2% Variable
Cancer + + +/-
Prognosis Worse with age Moderate Chronic - poor
Delta hepatitis agent, HDV – a defective RNA virus that co-infects and requires the helper function of HBV for its replication and expression
Co-infection can increase severity of acute hepatitis B but does not increase the likelihood of progression to chronic hepatitis
Superinfection occurs in patients who is already chronically infected with HBV (more severe liver disease versus co-infection)
90% chance of chronic infection if infected at birth despite being clinically silent
1% risk of chronicity if infection occurs in young adulthood and immunocompetent persons wherein clinical signs and symptoms are often present
broad, ranging from asymptomatic infection to debilitating disease or even end-stage, fatal hepatic failure
Fatigue- most common
persistent or intermittent jaundice
malaise and anorexia
progressive liver injury
hepatic decompensation (when superimposed on well-established cirrhosis)
do not distinguish adequately between histologically mild and severe hepatitis.
Aminotransferase elevations tend to be modest for chronic hepatitis B but may fluctuate in the range of 100–1,000 units.
alanine aminotransferase (ALT) tends to be more elevated than aspartate aminotransferase (AST); however, once cirrhosis is established, AST tends to exceed ALT
Levels of alkaline phosphatase activity tend to be normal or only marginally elevated.
In Severe Cases
moderate elevations in serum bilirubin [51.3–171 mol/L (3–10 mg/dL)] occur.
Hypoalbuminemia and prolongation of the prothrombin time
Hyperglobulinemia and detectable circulating autoantibodies are distinctly absent in chronic hepatitis B (in contrast to autoimmune hepatitis).
The laboratory abnormalities consist of : elevation of the ALT (normal to 200 IU/l) in up to 90% of patients. Transaminases, serum bilirubin, albumin, and gammaglobulin values
are mild to markedly elevated. autoimmune antibodies such as antinuclear antibody, anti-smooth
muscle antibody and antimitochondrial antibody may be present.
Sustained increases in the concentrations of the aminotransferases together with the presence of HBsAg for >6 months is regarded as indicative of chronic hepatitis.
http://www.who.int/csr/disease/hepatitis/whocdscsrlyo20022/en/index3.html#features
HBs Ag
AntiHBs
AntiHBc
HBe Ag
AntiHBe Interpretation
+ - IgM + -Acute Hepatitis BHighly infectivity
+ - IgG + -Chronic Hepatitis
BHighly Infectivity
HBs Ag
AntiHBs
AntiHBc
Hbe Ag
AntiHbe
Interpretation
+ - IgG - +
1. Late Acute or Chronic Hepatitis BLow infectivity
2. HBeAg negative(precore-mutant)Hepatitis B (chronic or rarely acute)
+ + + -/+ -/+
1. HbsAg of one subtype and heterotupic anti-HBs (common)
2. Process of seroconversion from HBsAg to anti HBs (rare)
HBsAg
AntiHBs
AntiHBc
HBe Ag
AntiHBe
Interpretation
- - IgM -/+ -/+1. Acute Hepatitis B2. Anti-HBc
“window”
- - IgG - -/+
1. Low levels Hepatitis B Carrier
2. Hepatitis B in remote past
HBsAg
AntiHBs
AntiHBc
HBeAg
AntiHBe
Interpretation
- + IgG - -/+ Recovery from Hepatitis B
- + - - -
1. Immunization with HBsAg (after vaccination)
2. Hepatitis B in remote past
3. False positive
Occurs in the end-stage of chronic hepatitis
Includes:AscitesEdema bleeding gastroesophageal variceshepatic encephalopathycoagulopathy hypersplenism
Associated with deposition of circulating hepatitis B antigen-antibody immune complexes
Common arthralgias arthritis
Rarepurpuric cutaneous lesions (leukocytoclastic
vasculitis)immune-complex glumerulonephritisgeneralized vasculitis (polyarteritis nodosa)
Management of chronic hepatitis B is directed at suppressing the level of virus replication
Treatment is suppressive rather than curative
3 drugs have been proven effective: Interferon (INF) α Lamivudine Adefovir dipivoxil
Mechanism of Action
Interferon
•induction of intracellular signals following binding to specific cell membrane receptors, resulting in inhibition of viral penetration, translation, transcription, protein processing, maturation, and release.•It also exerts immunomodulatory and antiproliferative activities
Lamivudine
inhibits HBV DNA polymerase by competing with deoxycytidine triphosphate for incorporation into the viral DNA, resulting in chain termination
Adefovir
a diester prodrug of adefovir, phosphorylated by cellular kinases to active diphosphate metabolite and then competitively inhibits HBV DNA polymerase to result in chain termination
Patients with Chronic Hepatitis B who are candidates for Antiviral Therapy
Clinical Feature Interferon
Lamivudine
Adefovir
Detectable markers of HBV replication
Yes Yes Yes
Normal ALT activity No No No
ALT <2 x upper limit of normal No No No
ALT >2 x upper limit of normal Yes Yes Yes
Immunocompetent Yes Yes Yes
Immunocompromised No Yes Yes
Adult acquisition (western) Yes Yes Yes
Childhood acquisition (asian) No Yes Yes
Compensated liver disease Yes Yes Yes
Decompensated liver disease No Yes Yes
“wild-type” HBeAg-reactive Yes Yes Yes
HBeAg-negative chronic hapatitis
Yes Yes Yes
Interferon refractory No Yes Yes
Comparison of the three drugs
Feature Interferon Lamivudine AdefovirRoute Injection Oral Oral
Duration of therapy 4 months ≥52 weeks ≥48 weeks
Tolerability poor good good
Nephrotoxicity none none Crea monitoring
HBeAg loss 33% 32-33% 23%
HBeAg seroconversion 18-20% 16-20% 12%
HBV DNA PCR negative
unlikely ~30% HBeAg +39% HBeAg -
21% HBeAg +52% HBeAg -
ALT normalization Confined to HBeAg responders
>40% HBeAg +>70% HBeAg -
50% HBeAg +72% HBeAg -
HBsAg loss during Rx 3-8% 2-4% Unlikely
HBsAg loss after Rx 80% over 9 yrs 23% over 2 yrs To be determined
Viral resistance None 15-30% @ 1 yr70% @ 5 yrs
None @ 1 yr2.5% @ 2 yrs
Natural History Reduced mortality, decompensation, HCC
To be determined To be determined
NONALCOHOLIC LIVER DISEASE
Group BTan, Genevieve - Tongo
Definitionrefers to a wide spectrum
of liver disease that include simple hepatic steatosis which over time can progress to NASH, with the subsequent development of fibrosis and cirrhosis
Although, histologically NAFLD resembles alcohol-induced liver disease, by definition NAFLD develops in patients who consume little or no alcohol.
Fauci et al. Harrison’s Principles of Internal Medicine 17 th ed. vol2. 2008.
Epidemiology
US and Europe
14-20% prevalence
US
NASH = 3%
Fibrosis due to NASH >40% of obese patients
Fauci et al. Harrison’s Principles of Internal Medicine 17 th ed. vol2. 2008.
Aminotransferases are mildly elevated 1.5 – 2x the upper limit of normal ALT > AST
Fatigue
Vague right upper quadrant discomfort
Clinical Features
Fauci et al. Harrison’s Principles of Internal Medicine 17 th ed. vol2. 2008.
Clinical Features
NASH is frequently seen in conjunction with other components of the metabolic syndromeHypertensionDMElevated lipidsObesity
Insulin resistanceMarker: Elevated ferritin levels
Fauci et al. Harrison’s Principles of Internal Medicine 17 th ed. vol2. 2008.
DiagnosisExclude alcoholic liver disease
< 20 g/d of alcohol be consumed
Lab TestLiver enzymes (ALT > AST)Hepatitis B and CIron studiesAutoimmune serology
Liver Biopsy
UltrasoundFauci et al. Harrison’s Principles of Internal Medicine 17 th ed. vol2. 2008.
Ultrasound
A sonogram of a fatty liver showing increased echotexture compared with the adjacent kidney (bright liver).
Liver Biopsy
Macrovesicular & Microvesicular Steatosis
Two patterns of hepatic steatosis are recognized:
(1) microvesicular steatosis: the cytoplasm is replaced by bubbles of fat that do not displace the nucleus; and
(2) macrovesicular steatosis: the cytoplasm is replaced by a large bubble of fat that displaces the nucleus to the edge of the cell.
Steatohepatitis
The histologic findings shown include macrovesicular steatosis, cytologic ballooning, Mallory bodies, and scattered lobular inflammation.
Mallory Body
Mallory body is shown within a ballooned hepatocyte
Pericellular Fibrosis
Pericellular fibrosis is shown (Masson's trichrome stain). The collagenous tissue (shown in blue) surrounds individual hepatocytes, producing a chicken-wire appearance.
Treatment
Fauci et al. Harrison’s Principles of Internal Medicine 17 th ed. vol2. 2008.
Treatment
Orlistat (Xenical) – reversible inhibitor of gastric and pancreatic lipase
Lipase break down fat in food so that it can be absorbed into the body.
So if Orlistat blocks this, then the fat can’t be absorbed. The Unabsorbed fat is excreted in the stool. Aid to weight loss.
Treatment
Thiazolidinedione – peroxisome proliferator-activated receptor (PPAR) gamma inhibitor
Improves insulin sensitivity within the adipocyte and skeletal muscle by upregulating specific protein kinases involved in decreasing fatty acid synthesis
Antioxidants – Vitamin E supplementation
Bariatric Surgery
Fauci et al. Harrison’s Principles of Internal Medicine 17 th ed. vol2. 2008.
Efforts should be directed to
encouraging the patient to
exercise and lose weight.
Treatment
Fauci et al. Harrison’s Principles of Internal Medicine 17 th ed. vol2. 2008.
AUTOIMMUNE HEPATITIS
Group CTorres - Ventura
Autoimmune HepatitisChronic disorder characterized by continuing hepatocellular necrosis and inflammation, usually with fibrosis
Capable of progressing to cirrhosis and liver failure
Prominent extrahepatic features of autoimmunity and seroimmunologic abnormalities
Autoimmune Hepatitis
Cell-mediated immunologic attack against liver cells progressive liver injury
Humoral immune mechanism extrahepatic manifestations of AIH
Predisposition is inherited
Liver specificity of the injury is triggered by environmental factors (chemical/viral)
Clinical Features insidious/abrupt onset
Young to middle-aged women
Marked hyperglobulinemia
High-titer circulating ANAs
Fatigue, malaise, anorexia, amenorrhea, acne, arthralgia, jaundice
Arthritis, maculopapular eruptions, erythema nodosum, colitis, pleurisy, pericarditis, anemia, azotemia, sicca syndrome
Ascites and edema, encephalopathy, hypersplenism, coagulopathy, variceal bleeding complications of cirrhosis
Laboratory FeaturesParameter
Values
ALT ↑ (100 – 1000 units)
AST
ALP Normal/↑
Serum Albumin
Normal/↓ in very active or advanced disease
Serum Globulin
N/↑ (>2.5 g/dL)
Bilirubin ↑ (51-171 µmol /L [3-10 mg/dL])
PT Prolonged (active or late phase)
RF present
ANA Homogenous stain
Liver BiopsySimilar to chronic viral hepatitisInterface hepatitis or piecemeal necrosis
Expanding portal tracts and mononuclear cell infiltrates (plasma cells) extending beyond the plate of periportal hepatocytes into the parenchyma
necroinflammatory activity characterizes the lobular parenchyma
“rosette” formation, thickened liver cell plates, regenerative “pseudolobules” hepatocellular regeneration
Common are septal fibrosis, bridging fibrosis and cirrhosis
Alvarez F, et al. International Autoimmune Hepatitis Report: review of criteria for diagnosis of autoimmune hepatitis. Journal of Hepatology. 1999; 31:929-38.
Hennes. E, et al. Simplified Criteria for the Diagnosis of Autoimmune Hepatitis. Hepatology. 2008; 48:169-176
Treatment
• initiated at 20 mg/d• in the US: initiation dose of 60 mg/d, tapered successively over the course of a month down to a maintenance level of 20 mg/d
Features found in AIH
Features found in the patient
Age and Gender Young to middle-aged females
50 year old female
Transaminases Elevated (100-1000 units)
Elevated
Clinical features arthralgia Joint pains
ANALYSIS
Group DViardo-Zuniga
BRIEF ReviewNORMAL VALUES (Widmann's Clinical Interpretation of
Laboratory Tests) ALT = 10-40 IU/L AST = 10-37 IU/L
Our case patient’s ALT = 90 IU/L
SALIENT FEATURES50 years old
Dialysis nurse
Elevated transaminase (ALT – 90 IU/L)
Rises in BP since 2003
Blood sugar elevated 2 years ago
joint pains
Body Mass Index = 30.47 OBESE CLASS
BP = 160/100
PR = 75/min regular
RR = 21/min
• Afebrile• Pink palpebral
conjunctivae, neck veins not distended
• Adynamic precordium, apex beat at 5th LICS MCL, *sustained, not diffuse, normal heart sounds, no murmurs
• Lungs/abdomen unremarkable. No pedal edema.
Differential DiagnosisChronic Viral Hepatitis
Autoimmune Hepatitis
Non-alcoholic liver disease
Chronic Viral Hepatitis
Strongest Risk Factor: Dialysis nurse (occupation)
High rates of HBV infection include health care workers exposed to blood.
Extrahepatic complications of chronic hepatitis B are associated with deposition of circulating hepatitis B Ag-Ab immune complexes. These include arthralgias and arthritis, which are common.“She occasionally takes Celecoxib for her joint pains”
Chronic Viral HepatitisAminotransferase elevations tend to be modest
for chronic hepatitis, may fluctuate in the range of 100-1000 units. Patient’s ALT is ALT = 90 IU/L, relatively near the
range for chronic hepatitis.
Autoimmune HepatitisMinimal aminotransferase elevations, serum
AST & ALT fluctuate in the range of 100-1000 units Patient’s ALT is ALT = 90 IU/L, relatively near the
range for chronic hepatitis.
Clinical features similar to chronic viral hepatitis. Fatigue, malaise, anorexia, acne, arthralgias, and jaundice are common. Patient did not manifest these symptoms.
PATIENTNON ALCOHOLIC FATTY
LIVER DISEASEelevated ALT noted on HPN work-
up (asymptomatic for liver disease)
incidentally discovered elevated liver enzymes
BMI = 30.47Obese, diabetic, non-alcoholic
patients
ALT = 90 IU/L (Normal: 10-40 IU/L)aminotransferases are only mildly
elevated(1.5-2 times upper limit of normal)
rises in BP since 2003, elevated blood sugar 2 years ago
frequently seen with other components of the metabolic syndrome (HPN, DM, elevated
lipids, and obesity), insulin resistance in virtually all patients
alcohol intake not noted< 20 grams per day alcohol to exclude alcohol liver disease
Most Likely DiagnosisNon-Alcoholic Fatty Liver Disease
“Minimal ALT elevations in asymptomatic blood donors rarely indicate severe liver disease; studies have shown that fatty liver disease is the most likely explanation.”