“LFTS” & Hepatitis Serology Flashcards
1
Q
typical values given in LFTs
A
Albumin Bilirubin Bilirubin Direct (conjugated)* Bilirubin Indirect (unconjugated)* Alkaline Phosphatase Total Protein ALT (Alanine aminotransferase) AST (Aspartate transaminase)
2
Q
we mat may see _____ on a typical LFTs
A
GGT
3
Q
which values must be ordered separately from a LFTS
A
PT, which is usually ordered with INR
and Labs indicative of liver infection (e.g. hepatitis labs)
4
Q
which two typical LFTs values are not included in the CMP and what must you order to obtain these values?
A
Bilirubin Direct (conjugated)* Bilirubin Indirect (unconjugated)* you must order a Hepatic function panel to get these values
5
Q
which value patterns would you expect to see in typical inflammation or hepatocellular damage
A
above normal ALT and AST
above normal Possible GGT
6
Q
In the case of inflammation/damage, which labs values would only rise if inflammation is severe
such as in acute hepatitis
A
above normal Bilirubin
above normal Bilirubin Direct
above normal Bilirubin Indirect
7
Q
which value patterns would you expect to see in typical case of cholestatis
such as in obstruction
A
above normal Bilirubin
above normal Bilirubin Direct (conjugated)
above normal Alkaline Phosphatase
possible above normal GGT
8
Q
clinical significance of GGT or Gamma-Glutamyl Transpeptidase
A
Used to determine source of Alkaline Phosphatase (ALP) elevation, whether is it bone or liver sourced
If GGT also elevated, source likely liver
9
Q
what lab value can be used as a marker of alcohol consumption
A
GGT, however it can be too sensitive and results can be elevated by small amounts of alcohol or various other drugs
10
Q
which value patterns would you use as an indication of reduced liver function
A
Albumin is low
Total protein is low
and PT, if ordered is, is prolonged (high)
11
Q
urine Urobilinogen in chloestasis is ______
A
decreased
12
Q
common cause of chloestasis related to the gallbladder
A
gallstones in the common bile duct
13
Q
medical term for gallstones in the common bile duct
A
choledocholithiasis
14
Q
patients with choledocholithiasis typically present with
A
pain specifically biliary colic
jaundice
clay colored stools
and cola colored urine
15
Q
other causes of choledocholithiasis
A
tumors such as in pancreatic cancer
16
Q
choledocholithiasis causes
A
an the extra-hepatic obstruction, resulting in inhibited hepatic bile flow into the duodenum
17
Q
results of an extra-hepatic obstruction
A
the conjugated bilirubin formed within the hepatocytes is unable to be excepted in the bile and is passed to the blood stream
18
Q
why does choledocholithiasis or extra-hepatic obstruction cause dark urine
A
Because conjugated bilirubin is water soluble (unlike unconjugated bilirubin), it can then be excreted by the kidneys into the urine. Urine looks dark and cola colored as a result
19
Q
typically the bilirubin is excerpted as bile and
A
is able to reach the intestine
20
Q
no urobilinogen & no stercobilin in the intestine causes
A
acholic white stools
21
Q
how should you test for a bile duct obstruction such as choledocholithiasis
A
test for bilirubin in the blood for more accurate results
22
Q
what type of obstruction is choledocholithiasis classified as
A
a post-hepatic obstruction
23
Q
when would you expect to see a isolated elevation of Indirect (Unconjugated) Bilirubin
A
often is it due to Gilbert Syndrome
24
Q
Gilbert syndrome
A
Benign condition
Results from defect in the promotor of the gene that encodes the enzyme uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1),
Usually only see Indirect Bilirubin in homozygotes so many pts present as isolated cases
During times of stress (e.g. dehydration, fasting, disease, menstruation, overexertion), can see episodes of jaundice
25
what does the UGT1A1 enzyme cause if working properly
which is responsible for the conjugation of bilirubin with glucuronic acid
26
how to diagnosis Gilbert syndrome
ruling out other causes of ↑Indirect Bilirubin
27
Alkaline phosphatase is derived from
liver and bone
| also a very small contribution is made from the intestines
28
which expensive test would indicate the source of an elevated Alk phos value
Alk phos isoenzymes
29
common cause of reduced liver function
cirrhosis or serve acute injury such as severe hepatitis or toxic insult like acetaminophen overdose
30
Cirrhosis results from
chronic liver disease
| due to chronic inflammation / hepatocellular damage causing scarring that can not be repaired
31
scarred or fibrotic livers
the liver does not function like healthy liver
| may be unable to detoxify harmful substances, “clean” blood, make vital proteins
32
cirrhosis patient signs & symptoms
Fatigue
Portal hypertension
Ascites
Jaundice (will see ↑Bili) – obstruction of flow, failure of hepatocyte conjugation, failure of excretion of bile [since unconjugated bilirubin is fat soluble – and cannot be excreted – it accumulates in fatty tissues (most notably the skin)]
Easy bruising / bleeding due to low platelets (thrombocytopenia) – that result from throbopoeitin, splenic sequestration, and increased destruction
Others
33
why do we see portal hypertension is cirrhosis
due to scarring obstructing flow
34
ascites and cirrhosis
causes an accumulation of fluid in the abdomen – partially due to portal hypertension
35
why do we see jaundice in cirrhosis patients
obstruction of flow causes failure of hepatocyte conjugation and failure of excretion of bile
since unconjugated bilirubin is fat soluble and cannot be excreted, it accumulates in fatty tissues, most notably the skin)]
36
why do we see easy bruising and bleeding in cirrhosis patients
due to low platelets (thrombocytopenia) that result from throbopoeitin, splenic sequestration, and increased destruction
37
how to diagnosis cirrhosis
a definitive diagnosis & staging requires liver biopsy
38
normal LFTs do not mean
the liver is normal
| Patients with normal ALT & AST levels can have significant liver disease
39
is ALT or AST more specific
ALT
40
risk factors for liver damage and disease
```
Family history
ETOH consumption
Obesity
Diabetes
Hyperlipidemia
Medications / Supplements
Autoimmune disease
```
41
hepatitis risk factors
```
IVDU / cocaine use
High-risk sexual behavior
Foreign travel
History of transfusion(s)
Tattoos
```
42
Medications and vitamins/herbals that can cause elevations in transaminases (ALT & AST)
```
Herbals/Vitamins
Ephedra
Kava
Vitamin A
ANY
```
```
Medications
Acetaminophen (often combined with opiates!)
Statins
Antifungals / Azoles
Antibiotics
Anti-TB drugs
NSAIDs
Tegretol
OTHERS
```
43
The easiest way to determine if a medication is responsible is to
stop it and see if the lab value returns to normal
44
Differential diagnosis for elevated transaminases (↑ALT & AST)
```
Hepatitis
HAV, HBV, HCV, autoimmune, others
Alcoholic liver disease
Fatty liver/ Nonalcoholic steatohepatitis
Medications
Hemochromatosis
Rare conditions
```
45
Differential diagnosis for elevated transaminases that are uncommon to have elevated transaminases
Celiac disease
| Hypothyroidism
46
rare conditions causing elevated transaminases
Alpha-1 antitrypsin deficiency
| Wilson’s disease
47
Modest elevations in ALT (& AST) are ____ and often ____
are common and often asymptomatic
48
when to worry about Elevated Transaminases
Other liver tests are abnormal
Clinical signs & symptoms of disease
greater than 3-5 fold elevation of any enzyme level
Persistently abnormal levels for > 6 months
49
Mildly elevated AST & ALT
less than 3 times normal level likely due to fatty liver or ETOH consumption
50
fatty liver is associated with
Obesity
Type 2 DM
Hyperlipidemia
51
Elevated AST
Alcoholic hepatitis
Common bile duct obstruction (choledocholithiasis) – will also see ↑Alk Phos & Direct Bili
Cholangitis (infection that can result from choledocholithiasis) – will also see ↑Alk Phos & Direct Bili
52
AST:ALT ratio of > 1 suggest
ETOH liver disease, especially if GGT > 2X normal
53
AST:ALT ratio of < 1 (ALT higher) suggest
Acute or chronic viral hepatitis
| NASH (Nonalcoholic steatohepatitis)
54
alk phos elevation usually more prominent than transaminase elevations in
cholestatic disease
55
fatty liver medical term
Hepatic steatosis
56
Fatty infiltration + associated inflammation creates
NASH a liver disease that is clinically and histologically indistinguishable from alcoholic steatohepatitis
57
NAFLD can lead to
cirrhosis, which can lead to liver failure and/or hepatocellular carcinoma
58
what causes the progression from steatosis to steatohepatitis
the etiology is unknown
59
prevalence of NAFLD (2008)
11% in population, accounting for 75% of chronic liver disease
60
NAFLD & NASH
| Risk Factors
```
Obesity
Hypertriglyceridemia / Dyslipidemia
Insulin resistance & DM
Medications
E.g. corticosteroids, estrogen, tamoxifen, amiodarone, anti-HIV medications
```
61
clinical symptoms of
NAFLD & NASH
most patients asymptomatic or have fatigue
elevated ALT or ALT & AST are simply noted on routine labs
hepatomegaly may also be appreciated during physical exam
labs may be normal
62
↓Albumin & ↑PT (protime) may occur with
advanced disease of NAFLD & NASH such as the progression to cirrhosis
63
Definitive diagnosis of NAFLD and NASH
Demonstration of hepatic steatosis by imaging or biopsy
Exclusion of significant alcohol consumption
Exclusion of other causes of hepatic steatosis`
64
initial test in NAFLD and NASH imaging
an ultrasound
echogenicity, ability to bounce sound, is increase
however this can only detect steatosis, not cirrhosis
65
other imaging and results for NAFLD and NASH
CT – decreased attenuation (reduced intensity of X-ray beams)
MRI – ↑fat signal
66
liver biopsy NAFLD and NASH
Need for liver biopsy determined by specialist may be needed if diagnosis is unclear or if you need to assess progression of disease (stage)
67
NASH (steatohepatitis) assoc. with _____ risk than NAFLD (Fatty Liver)
higher
68
General approach to management of NAFLD and NASH
Weight loss for patients who are obese
Hep A & B vaccinations
Avoid alcohol consumption
Treatment of risk factors for cardiovascular disease
69
Hereditary Hemochromatosis (HH)
Hereditary disorder of iron metabolism
| Autosomal recessive
70
Hereditary Hemochromatosis (HH) genetic mutation
Mutation of HFE gene is most common cause
Can be caused by other mutations that result in disordered iron regulation
Genetic mutation results in increased iron absorption from the gut→ leads to accumulation of iron in the: liver, kidney, pancreas, heart, adrenals, testes, pituitary
71
HFE gene encodes
HFE protein thought to be responsible for regulating the uptake of circulating iron
72
Hereditary Hemochromatosis (HH) prevalence
homozygotes in Caucasians in U.S. ≈ 0.5%; heterozygotes ≈ 10%
A different disorder of iron overload has been identified in African Americans – but HH is uncommon in African & Asian Americans
73
Hereditary Hemochromatosis Diagnosis
Clinical symptoms generally absent until the 5th decade
Symptoms appear earlier in men
Often diagnosed earlier due to family history or incidental ↑LFTs (ALT & AST) noted on routine lab
74
Hereditary Hemochromatosis symptoms
Symptoms initially non-specific – fatigue, malaise
Later manifestations (classic triad is cirrhosis, DM, bronze skin pigmentation)
Cirrhosis
Cardiac enlargement / cardiomyopathy
DM
Skin hyperpigmentation
75
steps to diagnosing HH
If patient has: ↑ALT & AST (& possibly Alk phos), symptoms, or 1st degree relative
Check serum transferrin saturation (transferrin is the main iron-binding protein) & ferritin (marker of iron storage)
If transferrin saturation (TS) < 45 (normal) & ferritin normal – no further evaluation
If TS ≥ 45 (high) and/or ferritin elevated – check for HFE genotype
76
Hereditary Hemochromatosis Prognosis
f not identified and managed – can result in cirrhosis leading to an hepatocellular carcinoma
As noted before, can also lead to DM, cardiomyopathy, hypopituitarism, hypogonadism, hypothyroidism, extra-hepatic cancer
Major cause of death is decompensated (severe) cirrhosis, HCC, DM, & cardiomyopathy
77
Hereditary Hemochromatosis Management
Therapeutic phlebotomy
No optimal regimen – usually removal of 1 unit of blood every 1-2 weeks
Avoid iron rich foods (e.g. red meat, vit. C)
Avoid insult to liver (no alcohol)
78
Autoimmune hepatitis
A chronic hepatitis characterized by autoimmune features, generally including presence of circulating autoantibodies
possible genetic susceptibility with environmental trigger
Affects all ethnic groups and can occur at any age
most commonly diagnosed in pts in their 40s or 50s
3.6 to 1 female predominance
79
Autoimmune hepatitis pervalence
Prevalence 11-25 per 100,000
80
Autoimmune hepatitis Diagnosis
Clinical manifestations & severity variable
Symptoms range from asymptomatic (no symptoms) to acute liver failure
Diagnosis based on characteristic serologic (blood) and histologic (biopsy) findings & by excluding other diseases
Liver biopsy may be needed if diagnosis uncertain
81
Autoimmune hepatitis labs
in addition to ↑ALT & AST (and other possible abnormal LFTs):
Increased total IgG (gamma-globulin) levels
+ ANA (antinuclear antibodies)
+ ASMA (anti-smooth muscle antibodies
+ others
82
autoimmune hepatitis managment
Refer to hepatologist
| Corticosteroid (prednisone) often prescribed
83
Wilson disease Background
Very rare hereditary disorder of cellular copper transport
| Autosomal recessive
84
Wilson disease genetic abnormality
leads to impaired biliary copper excretion → leads to accumulation of copper in several organs, most notably: liver, brain, cornea
85
Wilson disease prevalence
1 case in 30,000
86
Wilson disease Diagnosis
Variable age of onset (may be due to differences in mutation penetrance)
majority are diagnosed between ages 5 & 35
Children usu. present with liver disease / hepatitis 1st
Adults usu. present with neurologic symptoms 1st (dysarthria, gait abnormalities, dystonia, tremor, Parkinsonism, drooling), may have less liver involvement
Signs of liver disease variable – from asymptomatic to signs of steatosis to cirrhosis
Kayser-Fleischer rings in about ½ of pts with liver disease
87
Wilson disease Kayser-Fleisher ring
Fine pigmented granular deposits in the cornea
Color is brownish or gray-green
Detected by naked eye or slit lamp exam
Disappears with treatment
88
Wilson disease labs
↑ALT & AST
May have labs consistent with cirrhosis: ↓Albumin, ↑PT, thrombocytopenia (low platelets)
LOW ceruloplasmin
89
Wilsons disease refer to specialist for
definitive diagnosis
90
Wilson disease Prognosis
Untreated Wilson disease universally fatal – due to cirrhosis (or HCC) or neurologic disease
Prognosis for those who receive treatment is excellent
91
Wilson disease Management
By specialist
Lifetime therapy aimed at treating copper overload
D-penicillamine, a copper chelator (binds to copper for removal from body)
92
Approach to an asymptomatic patient with mildly elevated transaminases step one
Check for risk factors for hepatitis, liver damage, & conditions associated with NAFLD or NASH
Screen for Hepatitis C & B
ask about Alcohol, medications/supplements (if present, stop & recheck)
Obesity, dyslipidemia, DM → if present, screen for NAFLD/NASH with ultrasound
Can also check labs for hereditary hemochromatosis (especially if family history of liver disease) → if ↑transferrin saturation & ↑ferritin, refer to specialist for genetic testing
93
Approach to an asymptomatic patient with mildly elevated transaminases (ALT & AST) step 2
Consider other causes of elevated ALT & AST
Celiac disease
Hypothyroidism
Adrenal insufficiency
94
Approach to an asymptomatic patient with mildly elevated transaminases (ALT & AST) step 3
Consider screening for rare liver conditions
Autoimmune hepatitis → IgG, ANA, ASMA
Wilson disease → ceruplasmin (looking to see if it’s low)
may often be done by specialist
95
Approach to an asymptomatic patient with mildly elevated transaminases (ALT & AST) step 4
Ultimately may need specialty consult for definitive diagnosis
Gastroenterologist (GI) or hepatologist determine need for biopsy
96
Hepatitis A facts
causes “infectious / endemic hepatitis”
does not lead to chronic disease or to cirrhosis or (HCC)
Spread is fecal-oral route
Incubation period 10-50 days
Excreted in feces up to 2 week before clinical illness – rarely after first week of illness
In U.S. in 2015 acute symptomatic cases of HAV have gone down
97
HAV transmission
```
Household contacts
Daycare centers, nursing homes
Sexual contacts
Persons living in high risk areas
Persons traveling to high risk areas
Injection & non-injection drug users
```
98
HAV – clinical presentation
Fever, jaundice are main symptoms
>90% childhood infections asymptomatic
Just 25-50% adult infections asymptomatic
99
HAV prognosis
99% of cases recover completely
Very few pts experience permanent liver damage
Fatal for ~0.1% of individuals
100
HAV Post-exposure prophylaxis
```
Healthy individuals (12 months to 40 years old)
Vaccinate as soon as possible within 2 wks of exposure
```
For those < 12 months, > 40 y/o, or if there is a contraindication to vaccine, give immunoglobulin (IG)
101
HAV – prevention
Hygiene (hand washing)
Vaccinate children between 12-23 months of age
Consider for people 2 & older, anyone who wants protection
Vaccinate those who are at risk or at risk of complications from HAV
102
HAV high risk population
Persons living in/traveling to areas with intermediate/high rates of infection
Men who have sex with Men (MSM)
Injection & non-injection drug users
Those with chronic liver disease (e.g. NAFLD or NASH, hemochromatosis)
Those with clotting factor disorders
Contacts of people with HAV
103
HAV labs
ALT & AST can be in the hundreds or low thousands
also causes elevated bilirubin
Hep A Antibodies
104
If patient is IgM anti-HAV neg & IgG anti-HAV pos, this indicates
past infection and/or immunity
105
Hepatitis B (HBV)
Transmitted by blood, sexual contact, parenteral (injection) contact
HBV is a leading cause of cirrhosis & hepatocellular carcinoma worldwide
106
HBV prevalence
Affects ≈ 240 million persons
Worldwide 780,000/year die from chronic active HBV, related cirrhosis or HCC
In U.S. 850,000 – 2.2 million with chronic HBV
107
HBV risk factors
```
multiple sex partners 24%
other 23%
Injecting drug users 20%
Men who have sex with men 17%
sex contact 13%
household 3%
```
108
Acute HBV
Presence of signs/symptoms varies
Most children < 5 y/o & newly infected immunosuppressed adults are asymptomatic
30-50% of those ≥ 5 y/o have initial signs & symptoms – looks like hepatitis – fever, jaundice (N/V, dark urine)
Acute phase of hepatitis B rarely fulminant or fatal (only ≈ 0.5%)
109
chronic HBV clinical presentation and who gets affected
usu. asymptomatic until late disease
90% infected as infants
25-50% infected from ages 1-5
5% infected as adults
110
chronic HBV prognosis
Premature death due to cirrhosis or HCC
25% infected as children
15% infected after childhood
In U.S. ≈ 1800 / year die due to chronic HBV
111
acute HBV management
supportive
112
chronic HBV management
with antiviral medications – treatment usually is directed by a specialist
113
HBV prevention vaccination "more important"
```
Avoid high risk behaviors
important:
Vaccination
--All infants, beginning at birth
--All children aged <19 years who have not been vaccinated previously
--Persons with HIV infection
Persons seeking evaluation or treatment for a sexually transmitted disease
---Men who have sex with men
--Injection drug users
```
114
HBV prevention vaccination "less important"
Avoid high risk behaviors
important:
Vaccination
---Susceptible sex partners of hepatitis B surface antigen (HBsAg)-positive persons
---Sexually active persons who are not in a long-term, mutually monogamous relationship
--Susceptible household contacts of HBsAg-positive persons
--Health care and public safety workers at risk for exposure to blood or blood-contaminated body fluids
--Persons with end-stage renal disease, including predialysis, hemodialysis, peritoneal dialysis, and home dialysis patients
--Residents and staff of facilities for developmentally disabled persons
--Travelers to regions with intermediate of high rates of endemic HBV Persons with chronic liver disease
--Unvaccinated adults with diabetes mellitus who are aged 19 through 59 years (discretion of clinicians for unvaccinated)
115
HBV acute labs
↑ALT & AST (in the hundreds or thousands)
| When ALT & AST that high – will see high Bilirubin too
116
HBV chronic labs
↑ALT & AST (mildly elevated)
Diagnosis may be made by incidental ↑ALT and/or AST on routine lab
Do not see other abnormal labs until later disease (e.g. progression to cirrhosis)
117
antigen labs HBV
review from foundations
Hep B surface antigen (HBsAg): protein on surface of the virus (part of the virus).
Hep B surface antibody (anti-HBs): anti-HBs appears during recovery, usu. indicates recent infection or immunity; anti-HBs also develops in a person who has been successfully vaccinated.
Total Hep B core antibody (anti-HBc): appears at onset of symptoms in acute hepatitis B & persists for life; indicates previous or ongoing infection with HBV in undefined time frame.
IgM antibody to Hep B core antigen (IgM anti-HBc): indicates acute or recent infection with HBV (≤6 months).
Hep B e antigen (HBeAg): a secreted product of the nucleocapsid gene of HBV (part of virus) found in serum during acute and chronic hepatitis B; indicates that the virus is replicating and infected person has high levels of HBV.
Hep B e antibody (HBeAb or anti-HBe): produced by immune system temporarily during acute HBV infection or consistently during or after a burst in viral replication; spontaneous conversion from e antigen to e antibody (a change known as seroconversion) is a predictor of long-term clearance of HBV in patients undergoing antiviral therapy → indicates lower levels of HBV.
118
Hepatitis C
Transmitted primarily through large or repeated percutaneous exposures to infectious blood
Incidence in 2014 was ≈ 30,500 acute cases
Prevalence of chronic HCV in U.S. is ≈ 2.7-3.9 million
(more than HBV)
119
leading cause for liver transplants
chronic HCV
120
how is HCV transmitted frequently
Injection drug use (currently the most common means of HCV transmission in U.S.)
Receipt of donated blood, blood products, and organs (once a common means of transmission but now rare in the US since blood screening became available in 1992)
Needlestick injuries in health care settings
Birth to an HCV-infected mother (not spread through breast-feeding)
121
how is HCV transmitted infrequently
Sex with HCV-infected person
Sharing personal items contaminated with infectious blood, such as razors or toothbrushes
Invasive procedures, such as injections
122
acute HCV clinical presentation
20-30% who acquire HCV may become symptomatic, usu. mild
Can see fever, jaundice (N/V, dark urine)
Ave. time from exposure to symptom onset = 4-12 wks
123
acute HCV prognosis
25% will clear the infection
75% will develop chronic infection
of those chronically infected & not treated
65% will develop chronic ds
5-20% will develop cirrhosis over 20-30 yr period
1 in 5 will die from consequences of chronic infection (cirrhosis or HCC)
124
chronic HCV
usually asymptomatic until late disease
Symptoms of late liver disease
Fatigue/Malaise
Signs of liver not functioning such as ascites, jaundice
125
HCV management
Acute & Chronic HCV managed similarly
Depends on genotype (1-6) & subtype (there are > 50)
Genotype 1 is most common in U.S
126
HCV therapy
in 2011 a highly effective (curative) HCV protease inhibitor was released however it is very expensive
127
prevention of HCV
Avoid high risk behaviors & exposures
128
Prevention og HCV complications
```
Screen (with HCV Ab):
Everyone born 1945 to 1965
Injection drug users
Recipients of blood products before 1992
Persons with HIV
Persons with known exposure
```
Test* anyone with signs or symptoms, like an ↑ALT or AST
129
HCV labs
Start with HCV antibody
If +, check for HCV RNA
If HCV RNA virus is +, pt has HCV
if HCV RNA not present – may have cleared infection (most likely) or HCV antibody was a false positive.
If pt has HCV – refer to specialist who will do viral genotyping & may assess degree of liver damage prior to initiating treatment
130
does having Hep C in the past provide immunity for re infection
no, unlike other infections, having had Hep C does not provide immunity to re-infection
