4 Hepatitis and Liver Disease Flashcards
1
Q
AST/ALT 15-32 U/L
A
Normal
2
Q
AST/ALT 28-75 U/L
A
Cirrhosis
3
Q
AST/ALT 40-150
A
Hepatitis B/C (chronic)
4
Q
AST/ALT 150-500 U/L
A
EtOH hepatitis
5
Q
AST/ALT 300-3000 U/L
A
Hepatitis C, A, and B (acute)
6
Q
AST/ALT 500-10,000 U/L
A
“Shock Liver” or Acetaminophen toxicity
7
Q
Most common types of liver disease in the US
A
Non alcoholic fatty liver disease (17-33%)
Non alcoholic steatohepatitis (NASH) (5.7-17%)
Chronic Hep C (1.3%)
Alcoholic Liver Disease (0.8-1.3%)
Hemochromatosis (0.5%)
Chronic Hep B (0.4%)
8
Q
Hepatitis is a general term for …
A
Inflammation of the liver
9
Q
Hepatitis is reflected by …
A
Abnormal liver tests
Hepatocellular pattern (<10 x ULN)
Predominantly elevated ALT/AST (liver transaminases)
+/- elevated ALP (1/3 present with elevated ALP in NASH)
10
Q
AST:ALT ratio of >2 is suggestive of…
A
Alcoholic Liver Disease
11
Q
ALT>AST is suggestive of…
A
NASH (AST:ALT ratio usually <1)
Acute or chronic viral hepatitis
12
Q
Liver Diseases and associated liver enzyme elevation:
Hepatocellular Diseases (ALT/AST elevation predominates)
A
Nonalcoholic fatty liver disease Genetic hemochromatosis Wilson’s Disease Alpha 1 Antitrypsin Deficiency Autoimmune hepatitis Chronic/acute viral hepatitis Alcoholic Liver Disease Drug toxicity
13
Q
Liver Diseases and associated liver enzyme elevation:
Cholestatic Diseases (ALP/GGT elevation predominates)
A
PBC PSC Autoimmune Cholangiopathy Sarcoidosis Biliary Atresia Biliary Obstruction Drug Hepatotoxicity Drug Toxicity
14
Q
Non-Alcoholic Steatohepatitis (NASH) indicates fatty liver with ______ of liver w/ hepatocyte injury
A
Inflammation
15
Q
NASH has a worse prognosis than Fatty Liver because
A
Higher risk in developing fibrosis and cirrhosis
16
Q
Liver disease is considered non-alcoholic if …
A
<20g EtOH/day (less than 2-3 drinks/day)
17
Q
What are the two subtypes of NonAlcoholic Fatty Liver Disease?
A
Isolated Steatosis (NAFL) - fatty liver without injury or fibrosis of hepatocytes on bx
Non-Alcoholic Steatohepatitis (NASH) - fatty liver + inflammation = hepatocyte injury; bx +/- fibrosis
18
Q
Which type of non alcoholic fatty liver disease is more likely to progress to fibrosis/cirrhosis?
A
NASH - 34-42% will progress, sometimes rapidly (<2 years)
19
Q
Risk factors for nonalcoholic fatty liver disease
A
Abdominal obesity DM2 HLD (High TG and Low HDL) Metabolic Syndrome*** (strongest predictor) Genetic factors (PNPLA3, TM6SF2) Age
20
Q
Strongest predictive risk factor for NAFLD
A
Metabolic Syndrome
21
Q
How does NAFLD/NASH present?
A
Generally asymptomatic
Fatty infiltration incidentally seen on imaging
Exclusion of other causes and no significant EtOH Hx
22
Q
If obtained, a liver bx in a patient with NAFLD/NASH would show…
A
Steatosis (fat accumulation)
Inflammation +/- fibrosis
23
Q
Lab findings in NASH
A
Hepatocellular pattern
• Mild elevation ALT/AST rarely above 300 IU/Ml
Normal albumin, bilirubin, INR
Ferritin elevated = marker for inflammation
HLD
Glucose elevated (or dx of DM)
ALP elevated in 1/3, GGT frequently elevated too
+/- weakly positive autoimmune factors
24
Q
What is the main goal in managing NASH patients?
A
STOP PROGRESSION of cirrhosis
Exercise and weight loss are the cornerstones of management
25
How is body weight reduction associated with histological improvement in NASH?
>3% improves steatosis in 35-100% pts
7-10% NASH resolution (64-90% of patients)
≥10% Fibrosis regression seen (45% of patients)
26
In addition to weight loss and exercise, what else do you do to manage NASH?
Minimize EtOH and modify CVD risk factors
Control DM and HLD (statins OK in compensated cirrhosis)
Monitor LFT after implementation
Vaccinate for Hep A and Hep B if not immune
Liver bx
27
Is it ok to use statins in patients with NASH?
Yes, so long as they aren’t in decompensated state
Ok to use in compensated cirrhosis
28
Hereditary disorder of iron metabolism —> accumulation of iron in the liver, pancreas, heart, adrenals, testes, pituitary, skin, and kidney
Hereditary Hemochromatosis
Due to genetic mutation that results in increased GI absorption of iron
29
How is hereditary hemochromatosis typically found?
Family history or incidentally noted increase in AST/ALT
30
What ethnic group has the highest incidence of hereditary hemochromatosis?
Caucasians of Northern European Origin
31
Clinical presentation of hereditary hemochromatosis
Initially non-specific symptoms - fatigue, malaise, RUQ discomfort
Late manifestations (4th-5th decade of life) - hepatomegaly, hepatic insufficiency, cirrhosis, DM, impotence, arthralgia, bronze pigmentation of skin, cardiomegaly w/ or w/o CHF
32
What is bronze diabetes?
Triad of DM, bronze pigmentation of skin, cirrhosis
Associated with hereditary hemochromatosis
33
Lab findings for hereditary hemochromatosis
Modest elevation of AST, ALT, Alk Phos
Screen with a serum Fe and TIBC and ferritin
If transferrin sat ≥45 and/or ferritin >200ng/mL for men or >150 ng/mL in women, proceed to GI (HFE mutation analysis)
34
What is the treatment for hereditary hemochromatosis?
Therapeutic phlebotomy
35
How is hereditary hemochromatosis diagnosed?
Lab findings confirmed with genetic testing +/- liver biopsy
36
What is the goal of treatment for hereditary hemochromatosis?
To prevent cirrhosis from iron overload
37
What patient ed should you give in hereditary hemochromatosis?
Avoid Vit C and iron supplements
Avoid uncooked shellfish esp oysters
Avoid EtOH
Regular phlebotomy (managed by hematologist)
Risk of cirrhosis —> cirrhosis screen q6 months (US +/- AFP)
Genetic screening and iron testing advised for all 1st degree relatives
38
Who should be screened for hereditary hemochromatosis?
```
Elevated liver tests (AST/ALT)
Abnormal iron studies
First degree relative dx with HH
Evidence of liver disease
Suggestive symptoms of HH
```
39
Autosomal recessive mutation —> very rare hereditary disorder of copper metabolism
Wilson’s Disease
Results in decreased excretion of copper into bile and accumulation of copper in liver
40
In Wilson’s disease, once the liver’s capacity for copper is exceeded, what happens?
Copper is released into the bloodstream —> accumulates in brain, cornea, joints, kidney, heart, and pancreas
41
Clinical presentation of Wilson’s disease
Usually presents between ages 3-55
Predominantly hepatic, neurologic, and/or psychiatric Sx
• Tremor, dysarthria, incoordination/ataxia, Parkinsonism, personality/behavior changes
Kayser-Fleischer ring + neurologic manifestations is PATHOGNOMONIC
42
Fine pigmented (brownish or gray green) granular deposits in the cornea, detected either by naked eye or ophthalmoscope
Kayser-Fleischer rings
Together with neurologic manifestions, is pathognomonic for Wilson’s Disease
43
How is Wilson’s Disease diagnosed?
Mildly elevated AST/ALT with normal/low Alk Phos
Initial screen with serum ceruloplasmin (reduced in 85% of WD)
Opthal eval (for K-F rings)
24 hour urinary copper (increased)
Dx usually confirmed with liver biopsy +/- molecular testing
1st degree relative screening recommended
44
Treatment for Wilson’s Disease
Chelation with D-penicillamine and Trientine
Done by GI with specialized training in hepatology
45
What should you suspect in a non-smoker with emphysema at a young age (<45) or in neonatal cholestasis or childhood cirrhosis?
Alpha-1 antitrypsin deficiency
Genetic disorder characterized by decreased levels of alpha-1 antitrypsin production
46
What is alpha-1 antitrypsin?
Protects against tissue injury in the lungs and liver, and less often in the skin
47
Adults with alpha-1 antitrypsin deficiency are at risk for...
Severe lung disease and chronic liver disease
Increased risk with cigarette smoking and onset is accelerated
48
Infants and children with alpha-1 antitrypsin deficiency are more likely to present with...
Severe liver disease
49
Who should be screened for alpha-1 antitrypsin deficiency?
Emphysema in a young (<45) non smoker, esp if predominantly basilar changes on CXR
Adult-onset asthma
Clinical findings or hx of unexplained chronic liver disease
• Current or prior elevation of liver tests
• Patient with cirrhosis +/- portal HTN
Family Hx of emphysema and/or liver disease
Hx of panniculitis (skin manifestation)
50
How do you diagnose alpha-1 antitrypsin deficiency?
Mild elevation of AST/ALT
Serum alpha-1 antitrypsin decreased
AND
Alpha-1 antitrypsin phenotype/genotype
Rule out other causes +/- liver bx
51
What is the treatment for alpha-1 antitrypsin deficiency
Ultimately, liver transplant
Also, genetic counseling to explain likelihood of disease passing on to children
52
Clinical presentation of autoimmune hepatitis
Asymptomatic w/ elevated liver enzymes
Acute hepatitis +/- liver failure
Cirrhosis
Non-specific Sx:
Fatigue, malaise, anorexia, pruritis, abdominal pain, arthritis
53
1/3 of patients with autoimmune hepatitis present with...
Severe liver disease
Hepatomegaly/tenderness
Jaundice
Splenomegaly
Fever (low grade)
54
Serological markers for autoimmune hepatitis
```
More common in adults:
Antinuclear antibodies (ANA)
Anti-smooth muscle antibodies (ASMA)
Liver kidney microsomal antibody (LKMA)
Antibody to liver cytoskeleton (LKC-1), IgG
```
More common in children:
Anti-soluble liver antigen (SLA)
Anti-liver pancreas antigen (LPA)
55
Lab findings other than serological markers for autoimmune hepatitis
Elevated bilirubin
Elevated ALP
Elevated PT/INR
Albumin (decreased)
56
AST/ALT levels in acute autoimmune hepatitis are typically ...
7-10x ULN
57
How is autoimmune hepatitis diagnosed?
Serological markers w/ exclusion of viral/other causes and histologic findings on bx
58
Management of autoimmune hepatitis depends on...
Disease activity
Start with Prednisone +/- Azothioprine (Imuran) combination
59
Hep A is common in areas with...
Inadequate sanitation and limited access to clean water
High endemic areas include Asia and Africa
60
Route of transmission for Hep A
Fecal-Oral
Can be either person to person (lol rim jobs) or contaminated food/water
61
Does Hep A cause chronic infection?
Nope
62
How does Hep A present?
Children <6 more likely to be asymptomatic
Incubation period 15-50 days (avg 28 days)
Prodrome period (“flu-like”) - fever, malaise, anorexia, N/V, RUQ pain
Icteric Phase - jaundice, dark urine, pruritis, light colored stool (feels better but looks like shit)
Jaundice is usually one week after Sx begin
63
Most commonly observed abnormalities with Hep A
Hepatomegaly and Jaundice
64
What do your labs look like for Hep A
AST/ALT often >1000 or 15x ULN
Increased bilirubin
Increased ALP
+ IgM anti-HAV (Hep A antibody IgM) at onset of Sx
IgM (+) = acute infection
IgG (+) = implied immunity
65
Management of Hep A is usually...
Supportive Care
Fluids/rest, full recovery in nearly all patients by 6 months
66
Who should be hospitalized for Hep A?
Elderly
Multiple comorbidities
Underlying liver disease
Fulminant liver failure
67
How do you prevent Hep A?
Hand washing
Food handling precautions
Food prep/cooking with temps >185F
Chlorine is effective for inactivation of HAV
Notify local health dept and suggest vaccination of non-immune close contacts
Vaccine available
68
How is Hep B transmitted?
Blood/blood derived body fluids
```
Sharing razors, toothbrushes, etc
Contact with blood/open sores
Sex with infected partner
Parenteral contact (needles)
Peri-natal transmission (mother to child)
```
69
Hep B is the leading cause of _____ and ________ worldwide
Cirrhosis and Hepatocellular carcinoma
70
What is the incubation period for Hep B?
45-160 days
71
SSx of Hep B
N/V, RUQ pain, jaundice, malaise, arthralgias, fever
Increased bilirubin and alk phos
Significantly increased transaminases (>15xULN)
72
____% of adults but _____% of infants become chronic with Hep B
<5%
80-90%
73
How do you manage Hep B?
Supportive care - 95% of adults recover with immunity
+/- antiviral therapy (only in acute liver failure or protracted course)
74
Who should be hospitalized for Hep B?
Underlying liver disease
Multiple comorbidities
Signs of liver failure —> transplant center (<1%)
Older/elderly (disease more severe in age >60)
75
If you are vaccinated for Hep B, what antigens will you have?
anti-HBs (surface antigens)
76
If you’ve been infected with Hep B (current or previous infection), what antigens will you have?
Both anti-HBs (surface) and anti-HBc (core)
77
When will you see HepB e antigen?
Really high levels indicate current acute infection
78
How does Chronic Hep B present?
Most patients asymptomatic
Hep B surface antigen positive if >6 months
Transaminases elevated (very mild or normal)
79
Complications of chronic Hep B
Cirrhosis
Hepatocellular Carcinoma (HCC) can occur w/o cirrhosis
80
When does acute Hep B become chronic?
In immune compromised adults or if exposure as an infant or child <5 years
81
What labs you gonna get for Hep B?
HepB surface antigen (HBsAg)
Antibody to surface antigen (anti-HBs)
Antibody to Hep B core antigen (anti-HBc)
Hep B envelope antigen (HBeAg)
Antibody to Hep B envelope antigen (anti-HBe)
82
(+) HBsAg
Indicates active disease (acute or chronic)
83
(+) anti-HBs
Indicates immunity (from either vaccine or resolved infection)
84
(+) IgM anti-HBc
Indicates acute exposure to Hep B
85
(+) IgG anti-HBc
Indicates previous exposure to Hep B
86
(+) total anti-HBc
Indicates previous exposure
87
First detectable marker of Hep B infection
Hep B surface antigen (HBsAg)
Detectable in the blood 1-9 weeks after exposure
Hallmark of active infection (acute or chronic)
HBsAg (+) >6 months
88
HBsAg (+) >6 months
Chronic Hep B infection
89
_____ appears shortly after HBsAg detected
IgM anti-HBc
It’s the antibody to hep B core antigen
Indicates acute or recent infection
90
IgM anti-HBc can persist for ...
~4 months
91
IgG anti-HBc indicates...
Prior or resolving infection
Persists indefinitely
92
Hep B vaccine results in positive ...
Anti-HBs/HBsAb
The body makes antibody to surface antigen after exposed to surface antigen artificially
93
Which lab is used as an index of Hep B infectivity?
Hep B e-antigen (HBeAg)
It’s a marker for replication, associated with higher levels of HBV DNA
94
Antibody to Hep B e-antigen (anti-HBe) with HBeAg negative status indicates...
Lower levels of HBV DNA
Positive anti-HBe is a predictor of long term clearance of HBV
95
How is chronic Hep B managed?
GI will treat select patients with tenofovir/entecavir
Vaccinate for Hep A
Counsel on prevention precautions
HCC surveillance****
• All patients with or w/o cirrhosis
96
_____% of Hep C patients will develop chronic infection
75-85%
97
Most common cause of liver transplant with HCC
Hep C
Most common overall is NASH
98
Risk factors for Hep C infection
IVDU****, tattoos, piercings at unregulated facility
Recipient of clotting factors prior to 1987
Blood transfusion prior to 1992
HIV infection
Hemodialysis
Known exposure (needle stick)
Children born to HCV infected mothers (rare)
Sexual contact (rare but greater in MSM)
99
How does acute HCV infection present?
Usually 14-180 days from exposure
Asymptomatic in 70-85% of cases
10-20% —> jaundice, fatigue, fever, N/V, RUQ discomfort
• AST/ALT usually in 100s (but <300) - A/B much higher
• Bilirubin elevated
• (-) Hep C Ab w/ (+) RNA viral load OR (+) Heb C Ab with prior (-)
100
_____% of Chronic Hep C patients will develop cirrhosis within 20-30 years
10-20%
Most are asymptomatic and diagnosed via mildly elevated LFTs
101
Who should be screened for Hep C?
Persons born 1945-1965 w/o prior assessment of risk
Persons who received blood transfusion or transplant before July 1992 or clotting factor concentrates before 1987
Persons who have ever used injected or intranasal illegal drugs
Persons on long term dialysis
Children born to HCV positive women
Healthcare workers and public safety workers after needle sticks, sharps, or mucosal exposure to HCV positive blood
102
Diagnosis of Chronic Hep C
Elevated transaminases - will see varying ALT patterns
• Can be normal
• In cirrhosis AST can be greater than ALT
• In acute infection, will be in the 100s
LFTs can rise and fall
Most patients present in late stage disease, already with signs of cirrhosis
103
How do yo manage Hep C?
Avoid EtOH
Screen for Hep A/B and vaccinate if not immune
Discuss non-infected sexual partner testing
Discuss cure of Hep C does not preclude reinfection
Screen for HIV and other causes of liver disease and refer to GI for Tx
104
Patients with Hep C should receive regular _____ screen
HCC - +/- AFP regularly even after cure
105
How is Hep C treated now?
Direct Acting Anti-virals (DAA) x 8-12 weeks
Regime based on genotype, previous treatment, cirrhotic vs non-cirrhotic, viral load
106
Hep D is only seen in conjunction with...
Hep B - associated with more severe course
Presents with acute hepatitis symptoms
107
How is Hep D diagnosed?
Presence of Delta virus RNA with (+) HBsAg
Test for Hep D in all Hep B patients
108
How is Hep D treated?
Eradicate Hep B (refer to GI/hepatology
109
How is Hep E transmitted?
Fecal-oral
110
How does Hep E present?
Acute hepatitis symptoms similar to Hep A
Travel Hx to developing countries in last 1-2 months
Dx: Hep E RNA present
111
______ is fatal in approx 20% of infected pregnant women, otherwise, mostly benign
Hep E
More severe and greater mortality in 2nd and 3rd trimester
